Correlation of digital flow peak with spirometry in children with and without asthma.

INTRODUCTION: Spirometry and peak expiratory flow measurement (PEF) are combined during functional respiratory assessments. The new digital peak flow meter (DPM) evaluates the forced expiratory volume in the first second (FEV1) and PEF. OBJECTIVE: To compare lung function measurements using spirometry and DPM. METHODS: This cross-sectional analytical study assessed FEV1 and PEF in children with and without asthma. Statistical analysis was performed to assess the agreement between the measures using the intraclass correlation coefficient (ICC), Bland-Altman, and survival agreement plot. RESULTS: 125 (3-12 y) and 196 (6-18 y) children without and with asthma, respectively, were studied. In children without asthma, the ICC for FEV1 and PEF were 0.89 and 0.86, respectively, while the corresponding values were 0.87 and 0.79, respectively, in patients with asthma. The Bland-Altman method showed a difference of -0.4 to 0.5 for FEV1 in patients without asthma, with a tendency to increase as the FEV1 increased to a certain extent. In patients with asthma, the pattern was similar for FEV1, and the PEF had a greater dispersion than among those without asthma; however, a good agreement pattern was maintained. In the survival agreement plot, when accepting a tolerance of 0.150 mL for FEV1, there was an agreement of close to 55% in both groups. Likewise, when accepting a tolerance of 0.5 L/s for PEF, an agreement of close to 60% and 50% was observed in patients without and with asthma, respectively. CONCLUSION: DPM was effective as a measure of lung function in pediatric patients with and without asthma.

Fat mass to fat-free mass ratio and its associations with clinical characteristics in asthma.

BACKGROUND: Fat mass to fat-free mass ratio (FM/FFM) assesses the combined effect of the balance between fat mass and fat-free mass. AIMS: to evaluate the associations beetween FM/FFM and clinical outcomes in asthma and to compare clinical characteristics between individuals with higher and lower FM/FFM. METHODS: 128 participants with asthma underwent anthropometric, spirometry and bioelectrical impedance assessments. Physical activity in daily life (PADL) was assessed by the Actigraph for 7 days. Daily dose of inhaled medication, steps of pharmacological treatment, Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Hospital Anxiety and Depression Scale were also assessed. Participants were classified into two groups according to the 50th percentile of reference values for FM/FFM. RESULTS: Individuals with higher FM/FFM (n=75) used higher daily doses of inhaled corticosteroids, had worse lung function and fewer steps/day when compared to those with lower FM/FFM (n=53) (P≤0.021). Associations were found between absolute values of FM/FFM with lung function (FEV1 and FVC [liters]): R2=0.207 and 0.364;P<0.0001), and between the categories of lower or higher FM/FFM with steps of medication treatment (Cramer's V=0.218;P=0.016) and level of PADL (Cramer's V=0.236;P=0.009). The highest FM/FFM was a determining factor of physical inactivity (OR: 3.21;95%CI:1.17-8.78) and highest steps of pharmacological treatment (OR: 8.89;95%CI:1.23-64.08). CONCLUSION: Higher FM/FFM is significantly associated with worse clinical characteristics in individuals with asthma, such as higher doses of inhaled corticosteroids, worse lung function and fewer steps/day. Moreover, higher FM/FFM is a determining factor of physical inactivity and the highest steps of pharmacological treatment for asthma.

Níveis de eosinófilos circulantes e declínio da função pulmonar em doença pulmonar obstrutiva crônica estável: um estudo longitudinal retrospectivo / Circulating eosinophil levels and lung function decline in stable chronic obstructive pulmonary disease: a retrospective longitudinal study

RESUMO Objetivo Discute-se se eosinófilos no sangue (EOS) na doença pulmonar obstrutiva crônica (DPOC) são associados à evolução da doença. O objetivo deste estudo foi avaliar se a contagem diferencial de células brancas do sangue (CBS), os sintomas e o tratamento podem prever o declínio da função pulmonar e as exacerbações em pacientes com DPOC. Métodos Foram retrospectivamente examinados pacientes com DPOC estável submetidos a um monitoramento mínimo de três anos em nossas clínicas ambulatoriais. Coletaram-se informações sobre volumes pulmonares (VEF1 e CVF), contagens total e diferencial de CBS, exacerbações agudas de DPOC (número nos 12 meses anteriores ao início do estudo = EA-DPOC-B; e durante o monitoramento = EA-DPOC-F), status tabagístico e tratamento. Os declínios de VEF1 e EA-DPOC-F foram descritos empregando modelo linear generalizado e regressão binomial negativa com interceptação aleatória de nível 2, respectivamente. Os modelos incluíram contagens de eosinófilo e neutrófilo como potenciais preditores e foram ajustados de acordo com sexo, idade, status tabagístico, EA-DPOC-B, tratamento com broncodilatadores e corticosteroides inalados (CSI). Resultados 68 pacientes foram considerados, dos quais 36 para EOS- (< 170 células/μL, valor da mediana) e 32 para EOS+ (≥ 170 células/μL). ∆VEF1 foi maior em EOS+ do que em EOS- (34,86 mL/ano vs 4,49 mL/ano, p = 0,029). Após o ajuste em relação aos potenciais confundidores, as contagens de eosinófilos (β = 19,4; CI 95% 2,8,36,1; p = 0,022) e CSI (β = -57,7; CI 95% -91,5,-23,9; p = 0,001) foram positivamente e negativamente associadas ao declínio da função pulmonar, respectivamente. Os EOS não foram associados ao número de EA-DPOC-F. Conclusão Em pacientes com DPOC estável, o maior nível de EOS (embora em um intervalo regular) prevê um maior declínio de VEF1, enquanto os CSIs são associados a uma evolução mais lenta da obstrução do fluxo aéreo.

ABSTRACT Objective Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. Methods We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). Results Sixty-eight patients were considered, 36 bEOS- (<170 cells/μL, the median value) and 32 bEOS+ (≥170 cells/μL). ∆FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (β=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (β=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. Conclusion In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

Air pollution and indoor settings.

Indoor environments contribute significantly to total human exposure to air pollutants, as people spend most of their time indoors. Household air pollution (HAP) resulting from cooking with polluting ("dirty") fuels, which include coal, kerosene, and biomass (wood, charcoal, crop residues, and animal manure) is a global environmental health problem. Indoor pollutants are gases, particulates, toxins, and microorganisms among others, that can have an impact especially on the health of children and adults through a combination of different mechanisms on oxidative stress and gene activation, epigenetic, cellular, and immunological systems. Air pollution is a major risk factor and contributor to morbidity and mortality from major chronic diseases. Children are significantly affected by the impact of the environment due to biological immaturity, prenatal and postnatal lung development. Poor air quality has been related to an increased prevalence of clinical manifestations of allergic asthma and rhinitis. Health professionals should increase their role in managing the exposure of children and adults to air pollution with better methods of care, prevention, and collective action. Interventions to reduce household pollutants may promote health and can be achieved with education, community, and health professional involvement.

Evaluación de la respuesta aguda al broncodilatador en pacientes asmáticos sobrepesos y obesos / Evaluation of the acute response to the bronchodilator in overweight and obese asthmatic patients

Introducción: La obesidad está asociada al uso frecuente de medicación de rescate y padecer asma de mayor gravedad. Los obesos asmáticos tienen menor reactividad bronquial, sin embargo, existe información limitada sobre la magnitud de la reversibilidad aguda al broncodilatador (RAB). Objetivo: Evaluar la magnitud de respuesta aguda al broncodilatador en pacientes asmáticos sobrepesos y obesos. Métodos: Se realizó un estudio descriptivo transversal con 49 pacientes asmáticos sobrepesos y obesos atendidos en consulta externa del Hospital Neumológico Benéfico Jurídico (enero 2017˗ enero 2018) y se constató mediante espirometría la respuesta aguda al broncodilatador. Resultados: Predominó la edad (40-59 años), mayor asociación de padecer asma, poca mejoría con la aplicación del broncodilatador. El sexo femenino (20-59 años) presentó mayor número que el masculino y menor reversibilidad al broncodilatador. Los pacientes con antecedentes patológicos familiares de asma o atopia representaron 73,5 por ciento del total. El 76,5 por ciento de los obesos no presentó mejoría con la aplicación del broncodilatador. Predominó la categoría de gravedad persistente moderada. Conclusiones: El sexo femenino tiene más riesgo de padecer asma y no tener mejoría al aplicar el broncodilatador. Los obesos mayores de 40 años tienen mayor riesgo de no presentar reversibilidad aguda al broncodilatador. Los antecedentes patológicos familiares de asma o atopia y personales de otras enfermedades no predisponen a menor reversibilidad aguda al broncodilatador. La gravedad del asma no influye en la reversibilidad aguda al broncodilatador(AU)

Introduction: Obesity is associated with the frequent use of rescue medication and suffering from more severe asthma. Obese asthmatics have less bronchial reactivity, however, there is limited information on the magnitude of acute bronchodilator reversibility. Objective: To assess the magnitude of the acute response to the bronchodilator in overweight and obese asthmatic patients. Methods: A cross-sectional descriptive study was carried out in 49 overweight and obese asthmatic patients seen in the outpatient clinic at Benéfico Jurídico Pneumologic Hospital from January 2017 to January 2018, and the acute response to bronchodilator was verified by spirometry. Results: Age predominated (40-59 years), greater association of suffering from asthma, and little improvement with the use of bronchodilator. The female sex (20-59 years) showed greater number than the male and less reversibility to bronchodilator. Patients with family pathological history of asthma or atopy represented 73.5 percent of the total. 76.5 percent of the obese did not show improvement with the use of bronchodilator. The category of moderate persistent severity predominated. Conclusions: The female sex has greater risk of suffering from asthma and has no improvement when applying bronchodilator. Obese individuals over 40 years of age have higher risk of not having acute reversibility to the bronchodilator. Family pathological history of asthma or atopy and personal history of other diseases do not predispose to less acute reversibility of bronchodilator. The severity of asthma does not influence acute reversibility to bronchodilator(AU)

Clinical characteristics and outcomes in adult cystic fibrosis patients with severe lung disease in Porto Alegre, southern Brazil.

BACKGROUND: Advanced lung disease in adult cystic fibrosis (CF) drives most clinical care requirements. The aim was to evaluate outcome (time to death while in the study) in a cohort of adult CF patients with severe lung disease, and to determine the association among baseline patient characteristics and outcome. METHODS: A retrospective cohort study was performed and clinical records between 2000 and 2015 were reviewed. Severe lung disease was defined as forced expiratory volume in the first second (FEV1) < 30% of predicted. Outcomes of all patients, including their date of death or transplantation, were determined till January 1st, 2016. Clinical data were recorded at the entry date. RESULTS: Among 39 subjects included in the study, 20 (51.3%) died, 16 (41.0%) underwent bilateral lung transplantation, and 3 were alive at the end of the study period. Two variables were independently associated with death: body mass index (BMI ≥ 18.5 kg/m2) (HR = 0.78, 95% CI = 0.64-0.96 and p = 0.017) and use of tobramycin inhalation therapy (HR = 3.82, 95% CI = 1.38-10.6 and p = 0.010). Median survival was 37 (95% CI = 16.4-57.6) months. The best cut-off point for BMI was 18.5 kg/m2. Median survival in patients with BMI < 18.5 kg/m2 was 36 months (95% CI = 18.7-53.3). CONCLUSION: Median survival of CF subjects with FEV1 < 30% was 37 months. BMI and tobramycin inhalation therapy were independently associated with death. Median survival in patients with BMI < 18.5 kg/m2 was significantly lower than in patients with BMI ≥ 18.5 kg/m2. The association of tobramycin inhalation with death was interpreted as confounding by severity (use was reserved for advanced lung disease).

FEV1/FEV6 y FEV6 una alternativa para FEV1/FVC y FVC en la detección de obstrucción de vías respiratorias / FEV1/FEV6 and FEV6 an alternative for FEV1/FVC and FVC in the detection of airway obstruction

INTRODUCCIÓN: el objetivo de este estudio fue verificar si los puntos de corte fijos y el límite inferior de lo normal (LLN) para el volumen espiratorio forzado en un segundo (FEV1) y el volumen espiratorio forzado en 6 segundos (FEV6) FEV1/FEV6 y el FEV6 son una medida alternativa para el FEV1 y la capacidad vital forzada (FVC), FEV1/FVC y la FVC en la detección de la enfermedad pulmonar obstructiva crónica (EPOC), en una muestra de pacientes del oriente boliviano. MÉTODOS: se analizaron un total de 92 pruebas espirométricas, 66 varones y 26 mujeres con riesgo de EPOC. La población del estudio incluyó a residentes de la ciudad de Santa Cruz de la Sierra-Bolivia (ciudad cosmopolita) de 35 a 90 años de edad. RESULTADOS: la sensibilidad y la especificidad fueron del 97,0% y el 96,9%, respectivamente, cuando se compararon los valores de corte fijos de FEV1/FEV6 de 0,73 con los de FEV1/FVC < 0,7 como regla estándar, según las recomendaciones del global obstructive lung diseases (GOLD) para detectar la obstrucción de las vías respiratorias. La sensibilidad y la especificidad fueron de 93,4% y 81,2%, respectivamente, cuando el LLN de FEV1/FVC y FEV1/FEV6 fueron utilizados. CONCLUSIONES: en conclusión, el FEV6 es un sustituto válido de la CVF para detectar la obstrucción de las vías respiratorias, ya sea utilizando puntos de corte fijos o el LLN. Se necesitan más estudios para verificar estos resultados en una población más grande y para establecer los valores predictivos espirométricos locales.

INTRODUCTION: the aim of this study was to verify if fixed cut-off points and lower limit of normal (LLN) for forced expiratory volume in one second (FEV1)/FEV6 and FEV6 as an alternative for FEV1/forced vital capacity (FVC) and FVC are valid for the detection of obstructive lung disease in a sample of Bolivian subjects. METHODS: a total of 92 spirometric consecutive tests from subjects, 66 males and 26 females at risk for COPD were analyzed. The study population included residents of city Santa Cruz de la Sierra, (Bolivia) aged from 35 to 90 yrs., from various ethnical origins (cosmopolitan city). RESULTS: sensibility and specificity were 97.0% and 96.9%, respectively when fixed cut-off values of FEV1/FEV6 of 0.73 was compared to FEV1/FVC<0.7 as standard, according to GOLD recommendations to detect airway obstruction. Sensibility and specificity were 100% and 89.5%, respectively when LLN of FEV1/FVC and FEV1/FEV6 were used. CONCLUSIONS: in conclusion, FEV6 is a valid surrogate for FVC to detect airway obstruction, either using fixed cut-off points or LLN. Further study is needed to verify these results in a larger population and to establish local spirometric predicted values

Factors that affect blood eosinophil counts in a non-asthmatic population: Post hoc analysis of data from Brazil.

BACKGROUND: Improved understanding of the normal range of blood eosinophil counts (BEC) and conditions that influence them in non-asthmatic individuals should allow more accurate estimation of the threshold at which eosinophilic disease should be considered, diagnosed, and treated. This analysis investigated the impact of atopy, smoking, and parasitic infection on BEC. METHODS: This was a post hoc analysis of non-asthmatic subjects from a case-control study (CONEP 450/10) conducted at the Program for Control of Asthma in Bahia (ProAR). Participant BECs were measured at baseline; correlations between predefined risk factors and BEC were assessed via univariate and stratified analysis. RESULTS: Of the 454 participants included, 3% were helminth parasite-positive, 18% were non-helminth parasite-positive; and 450 had BEC data. The median (interquartile range [IQR]) BEC was 152 (96, 252) cells/µL. Any positive skin prick test, elevated total immunoglobulin E, allergic rhinitis, and being a current smoker were all individually associated with higher BEC (p < 0.05) compared with BEC in participants without these factors, but having a non-helminthic parasitic infection was not. Participants with all 4 risk factors that were associated with higher BEC had a median (IQR) BEC of 192 cells/µL (94, 416) versus 106 cells/µL (70, 164) for those with no risk factors. CONCLUSIONS: In non-asthmatic subjects, atopy, allergic rhinitis, and current smoking status were associated with higher BEC compared with subjects without these factors, but BEC values were well below the threshold commonly accepted as normal. Therefore, BEC should be interpreted in the context of an individual's medical conditions and other BEC-influencing factors.

Whole-Genome Sequencing Identifies Novel Functional Loci Associated with Lung Function in Puerto Rican Youth.

Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma.

The Relationship of IL-8 and IL-10 Myokines and Performance in Male Marathon Runners Presenting Exercise-Induced Bronchoconstriction.

At present, it is unclear which exercise-induced factors, such as myokines, could diminish the negative impact of the reduction in pulmonary function imposed by the exercise in question. In this study, we aim to evaluate the prevalence of exercise-induced bronchoconstriction (EIB) and also to investigate the effect of myokines in the performance of marathon runners presenting EIB or not. Thirty-eight male recreational marathon runners (age 38.8 [33-44], height 175.7 [172.0-180.3]; weight 74.7 [69.3-81.6]) participated in this study, and through spirometry tests, a prevalence of 23.6% of EIB was found, which is in agreement with the literature. The volunteers who tested positive to EIB (EIB+) presented lower maximum aerobic capacity compared to those who tested negative (EIB-) (EIB+ 44.02 [39.56-47.02] and EIB- 47.62 [44.11-51.18] p = 0.03). The comparison of plasma levels of IL-1ß (EIB+ p = 0.296, EIB- p = 0.176, EIB+ vs. EIB- baseline p = 0.190 immediately after p = 0.106), IL-4 (undetectable), IL-6 (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.301 immediately after p = 0.614), IL-8 (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.110 immediately after p = 0.453), IL-10 (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.424 immediately after p = 0.876) and TNF-α (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.141 immediately after p = 0.898) were similar in both groups 24 h before and immediately after the marathon. However, negative correlations were found between the marathon finishing time and the levels of IL-8 (r = -0.81, p = 0.022), and IL-10 (r = -0.97, p ≤ 0.001) immediately after completing the marathon. In conclusion, for the first time, it is shown that the myokines IL-8 and IL-10 are related to improvement of the performance of marathon runners presenting EIB.

COPD: Gaps in the GOLD Recommendations and Related Imperative Research Needs.

The GOLD 2020 updates added more lucidity on the treatment of COPD. However, few diagnostic dilemmas still exist. Research is needed on the use of the CAT score in assessing symptoms for the diagnosis of COPD. Further work-up is needed on diagnostic instability of spirometry, and diagnostic role of the lower limit of normal (LLN) criteria, slow vital capacity (FEV1/VC), forced inspiratory vital capacity (FEV1/FIVC), and rapid FEV1 decline. Incorporating parameters of lung hyperinflation and exercise capacity in the COPD diagnostic criteria might add value in its diagnosis and management. GOLD's approach towards routine CT imaging needs to be reviewed. Establishing a "pre-COPD" stage can be helpful in the early diagnosis and intervention to reduce the rapid lung function decline among at-risk individuals. The use of mMRC score as a surrogate to assess the overall severity of COPD related symptoms should be reviewed. The therapeutic guidance role of sputum eosinophils should be studied in patients with intermediate and low blood eosinophil counts.

Longitudinal Analysis of Pulmonary Function in Survivors of Congenital Diaphragmatic Hernia.

OBJECTIVE: To analyze longitudinal trends of pulmonary function testing in patients with congenital diaphragmatic hernia (CDH) followed in our multidisciplinary clinic. STUDY DESIGN: This was a retrospective cohort study of CDH patients born between 1991 and 2013. A linear mixed effects model was fitted to estimate the trends of percent predicted forced expiratory volume in 1 second (FEV1pp), percent predicted forced vital capacity (FVCpp), and FEV1/FVC over time. RESULTS: Of 268 patients with CDH who survived to discharge, 119 had at least 1 pulmonary function test study. The FEV1pp (P < .001), FVCpp (P = .017), and FEV1/FVC (P = .001) decreased with age. Compared with defect size A/B, those with defect size C/D had lower FEV1pp by an average of 11.5% (95% CI, 2.9%-20.1%; P = .010). A history of oxygen use at initial hospital discharge also correlated with decreased FEV1pp by an average of 8.0% (95% CI, 1.2%-15.0%; P = .023). CONCLUSIONS: In a select cohort of CDH survivors, average pulmonary function declines with age relative to expected population normative values. Those with severe CDH represent a population at risk for worsening pulmonary function test measurements who may benefit from recognition and monitoring for complications.

Randomized Clinical Trial Comparing Breath-Enhanced to Conventional Nebulizers in the Treatment of Children with Acute Asthma.

OBJECTIVE: To compare the efficacy of a breath-enhanced and a conventional jet nebulizer in the treatment of children with moderate to severe acute asthma. STUDY DESIGN: We enrolled subjects between 6 and 18 years of age presenting to the emergency department (ED) with acute asthma and an initial forced expiratory volume in 1 second (FEV1) <70% of predicted. We excluded patients with chronic disease, who required immediate resuscitation, or failed spirometry. Subjects were randomized to breath-enhanced or conventional jet delivery of a 5-mg albuterol treatment. Our primary outcome was change in FEV1, and secondary outcomes included change in clinical asthma scores, ED length of stay, disposition, and side effects. Student t test and multivariable linear regression were used to evaluate the primary outcome. RESULTS: In total, 497 patients were assessed for eligibility with 118 enrolled and 107 subjects available for analysis of the primary outcome. Improvement in FEV1 was significantly greater with conventional jet nebulizer (mean ΔFEV1 +13.8% vs +9.1%, P = .04). This difference remained significant after adjustment for baseline differences. Subgroup analysis of 57 subjects with spirometry meeting American Thoracic Society/European Respiratory Society guidelines yielded similar results (mean ΔFEV1 +14.5% vs +8.5%, P=.03). There were no significant differences in clinical asthma scores, ED length of stay, disposition, or side effects. CONCLUSIONS: Albuterol delivered via conventional jet nebulizer resulted in significantly greater improvement in FEV1 than albuterol delivered by breath-enhanced nebulizer, without significant differences in clinical measures. Conventional jet nebulizers may deliver albuterol to children with acute asthma more effectively than breath-enhanced nebulizers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02566902.

Declining Lung Function and Cardiovascular Risk: The ARIC Study.

BACKGROUND: Pulmonary dysfunction predicts incident cardiovascular disease (CVD). OBJECTIVES: The purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke. METHODS: Among 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV1) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV1 or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking. RESULTS: The mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV1 and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV1 most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV1 was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015). CONCLUSIONS: A rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF.

Caracterización espirométrica de pacientes con fibrosis quística / Spirometric caracterization of cystic fibrosis patients

INTRODUCCIÓN: El pronóstico de los pacientes con fibrosis quística (FQ) ha mejorado en forma notable. La evaluación de la progresión de la enfermedad se basa en la medición del Volumen Espirado al primer segundo (VEF1). OBJETIVOS: 1. Describir volúmenes y flujos espiratorios forzados y comparar su interpretación según diferentes patrones de referencia (Knudson, multiétnicas Global Lung Initiative, Gutiérrez); 2. Comparar evolución de VEF1 según diferentes patrones de referencia; 3. Describir respuesta a broncodilatador. PACIENTES Y MÉTODO: Estudio retrospectivo de fichas clínicas y espirometrías de pacientes con FQ controlados en Hospital Dr. Sótero del Río. Se obtuvo antecedentes demográficos, resultados de prueba de sudor, estudio genético, estudio bacteriológico. Se evaluó respuesta a broncodilatador (salbutamol 400 ugr), considerando significativo un aumento en 12% en el VEF1. El valor de cloro en sudor se obtuvo mediante método de Gibson y Cooke. Se registraron: Capacidad Vital Forzada (CVF), Volumen Espirado al primer segundo (VEF1) y relación VEF1/CVF. Para graficar la progresión del VEF1 en el tiempo y las curvas teóricas de GLI, Knudson y Gutiérrez, se utilizó el software de libre distribución R versión 3.3.1. RESULTADOS: Se incluyeron 14 pacientes, 7 varones, edad entre 6 y 24 años, mediana 15 años, me diana índice de masa corporal (IMC) 18,15 (rango 14,6-23,3), mediana cloro en sudor 76 mEq/l (rango 50,2- 119), 7 pacientes con al menos 1 mutación F508del. Al utilizar fórmulas predictivas multiétnicas y de Gutiérrez, el compromiso de la función pulmonar ocurría con anterioridad en relación al uso de ecuaciones de Knudson. Ninguno de los pacientes presentó respuesta significativa a broncodilatador. CONCLUSIÓN: El grupo de pacientes descritos presenta en su mayoría compromiso funcional respiratorio y no tiene respuesta a broncodilatador. La interpretación del compromiso funcional respiratorio varía según los valores teóricos utilizados.

INTRODUCTION: The prognosis of patients with cystic fibrosis (CF) has remarkably improved. The as sessment of the disease progression is based on the measurement of the FEV1 (Forced Expiratory Volume in one second). OBJECTIVES: 1. To describe forced expiratory flows and volumes and com pare their interpretation according to different reference standards (Knudson, Gutiérrez, and multi ethnic GLI); 2. To describe bronchodilator response. Patients and Method: The medical records and spirometries of all patients with CF controlled at the Dr. Sotero del Rio Hospital were reviewed. Demographic background, sweat test results, genetic study , and bacteriological study were obtained. In addition, Forced Vital Capacity (FVC) was recorded as well as FEV1 and FEV1/FVC ratio. RESULTS: Data from 14 patients, were analyzed, seven males, aged 6-24 years, median 15 years, median BMI 18.15 (range 14.6-23.3), median sweat chloride test 76 mEq/l (range 50,2-119 mEq/l), seven patients with at least one F508del mutation. Using multi-ethnic and Gutierrez predictive formulas, lung function involvement occurred previously in relation to the use of Knudson equations. None of the patients had a significant bronchodilator response. CONCLUSION: The group of patients descri bed mostly presents functional respiratory involvement and had no bronchodilator response. The interpretation of functional respiratory involvement varies according to the theoretical values used.

Cambios en la puntuación del índice BODE en pacientes con enfermedad pulmonar obstructiva crónica antes y después de rehabilitación pulmonar / BODE Index Score Changes in COPD Patients Before and After Pulmonary Rehabilitation / Mudanças na pontuação do índice BODE em pacientes com DPOC, antes e depois de reabilitação pulmonar

Resumen Introducción: la rehabilitación pulmonar ha sido avalada como herramienta de tratamiento en la enfermedad pulmonar obstructiva crónica (EPOC). Aunque existen varios programas en nuestro medio, son escasos los reportes que evalúen el impacto de estos. El índice BODE es una escala multidimensional que refleja el impacto de los factores pulmonar y extrapulmonar en el pronóstico y la sobrevida; la rehabilitación pulmonar mejora algunos componentes del índice. El objetivo fue describir los cambios en la puntuación del índice BODE en pacientes con EPOC, antes y después de asistir a un programa de rehabilitación pulmonar. Materiales y métodos: estudio descriptivo, retrospectivo-longitudinal. Se seleccionaron registros diligenciados en el 2009 y el 2010. Se incluyeron 24 pacientes con EPOC que asistieron durante ocho semanas a un hospital nivel III de la ciudad de Cali, Colombia. Se realizó el análisis descriptivo que incluyó frecuencias, medidas de tendencia central y dispersión. El análisis inferencial se basó en la comparación de la evaluación inicial y final de las variables de estudio. Resultados: la puntuación total del índice BODE, la tolerancia al esfuerzo, la medida con test de caminata y la disnea medida con la escala del Modified Medical Research Council (MCRM) tuvieron reducciones significativas (p > 0,05). Conclusiones: se observó que la rehabilitación pulmonar reduce la puntuación del índice BODE en pacientes con EPOC.

Abstract Introduction: Pulmonary Rehabilitation has been endorsed as a treatment tool in Chronic Obstructive Pulmonary Disease. Although there are several programs in our environment, there are few reports that evaluate their impact. The BODE Index is a multidimensional scale that reflects the impact of lung and extrapulmonary factors on prognosis and survival; Pulmonary rehabilitation improves some components of the BODE index. The objective was to describe changes in BODE index score in patients with COPD, before and after attending a PR program. Materials and methods: Descriptive, retrospective-longitudinal study. Records were selected in the years 2009-2010. We included 24 patients with COPD who attended for 8 weeks in a level III hospital in the city of Cali-Colombia. Descriptive analysis was performed, including frequencies, measures of central tendency and dispersion. The inferential analysis was based on the comparison of the initial and final evaluation of the study variables. Results: Total BODE score, effort tolerance, measured with walking test and dyspnea measured with the Modified Medical Research Council scale, had significant reductions (p> 0.05). Conclusions: It was observed that Pulmonary Rehabilitation reduces the score of the BODE index in patients with COPD.

Resumo Introdução: a reabilitação pulmonar tem sido aprovada como ferramenta de tratamento na Doença Pulmonar Obstrutiva Crônica. Ainda que existem vários programas em nosso meio, são escassos os reportes que avaliem o impacto dos mesmos. O índice BODE é uma escala multidimensional que reflete o impacto dos fatores pulmonar e extrapulmonar no prognóstico e a sobrevida; a reabilitação pulmonar melhora alguns componentes do índice. O objetivo foi descrever as mudanças na pontuação do índice BODE em pacientes com DPOC, antes e depois de assistir a um programa de Reabilitação pulmonar. Materiais e métodos: estudo descritivo, retrospectivo-longitudinal. Selecionaram-se registros preenchidos nos anos 2009-2010. Se incluíram 24 pacientes com DPOC que assistiram durante 8 semanas em um hospital nível III da cidade de Cali, Colômbia. Se realizou uma análise descritiva que incluiu frequências, medidas de tendência central e dispersão. A análise inferencial baseou-se na comparação da avaliação inicial e final das variáveis de estudo. Resultados: a pontuação total do índice BODE, a tolerância ao esforço, medida com teste de caminhada e a dispneia medida com a escala Modified Medical Research Council, tiveram reduções significativas (p>0,05). Conclusões: Se observou que a Reabilitação Pulmonar reduz a pontuação do índice BODE em pacientes com DPOC.

Increased rate of osteoporosis, low lean mass, and fragility fractures in COPD patients: association with disease severity.

A very high rate of osteoporosis, fractures, and low lean mass was observed in patients with chronic obstructive pulmonary disease (COPD). Disease severity was associated with bone and muscle adverse outcomes, while age ≥ 63.5 years old, low lean mass, higher iPTH, and a T-score below - 2.5 were all associated with higher risk of fracture. INTRODUCTION: Osteoporosis is frequently neglected in patients with COPD. We aimed at evaluating the rate of osteoporosis, fractures, and low lean mass in patients with COPD. METHODS: Ninety-nine patients with COPD (53 women, 64.5 ± 9.6 years old, and 46 men, 65.9 ± 8.0 years old) underwent bone densitometry (DXA) with body composition analyses. Healthy individuals (N = 57) not exposed to tobacco matched by sex, age, and body mass index (BMI) were used as controls. Spirometry, routine laboratory workout, and conventional thoracolumbar radiography surveying for vertebral deformities were performed in all patients. RESULTS: Osteoporosis was found in 40.4% of the COPD patients against only 13.0% of the healthy controls (p = 0.001). Vertebral fractures were seen in 24.4% of the men and 22.0% of the women with COPD. Disease severity (GOLD 3 and 4) was significantly associated with higher risk of vitamin D deficiency (p = 0.032), lower BMD (both men and women at all sites), higher frequency of osteoporosis (in women at all sites), lower skeletal mass index, and higher rate of low lean mass (in both men and women) than healthy controls and COPD patients with milder disease (GOLD 1 and 2). Age was a main predictor of vertebral fractures (OR = 1.164 (1.078-9.297); p < 0.001), while high plasma iPTH (OR = 1.045 (1.005-1.088); p = 0.029) and low ALM (OR = 0.99965 (0.99933-0.99997); p = 0.031) were predictors of non-vertebral fractures. CONCLUSION: Highly prevalent in COPD, osteoporosis and low lean mass were associated with FEV1% < 50%. Age, low lean mass, high iPTH, and low bone mass were all significantly associated with fractures in COPD patients.

Spirometric instability - another hurdle in achieving real-world COPD diagnostic criteria?

Globally, mortality, morbidity and the economic burden of chronic obstructive pulmonary disease (COPD) are on the rise. In addition, its diagnosis continues to pose challenges to the physicians, which is compounded further by its new feature "spirometric instability." Based on the findings from the two recent observational studies, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended repeat spirometry for the individuals with a fixed ratio between 0.6 and 0.8. In this perspective, we discuss the uncertainties and consequences of this critical update in the 2018 GOLD report.

Metabolomic profiling of lung function in Costa-Rican children with asthma.

BACKGROUND: The development of novel therapeutics and treatment regimens for the management of asthma is hindered by an incomplete understanding of its heterogeneous nature and pathophysiology. Metabolomics can provide an integrated and global profile of a biological system in a dysregulated state, making it a valuable tool to identify biomarkers along the disease development pathway and to understand the biological mechanisms driving that pathway. METHODS: Liquid chromatography-mass spectrometry metabolomic profiling was conducted on plasma samples provided at recruitment for 380 children with asthma from the 'Genetic Epidemiology of Asthma in Costa Rica Cohort'. Metabolites associated with three clinical characteristics of asthma severity (i) airway hyper-responsiveness (AHR) (ii) percent-predicted forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and (iii) FEV1/FVC post-bronchodilator were identified and their discriminatory ability assessed. Metabolite set enrichment analyses was applied to explore the biology underlying these relationships. RESULTS: AHR was associated (p<0.05) with 91 of 574 metabolites (15.9%), FEV1/FVC pre-bronchodilator with 102(17.8%), and FEV1/FVC post-bronchodilator with 155 (27.0%). The findings suggest that these characteristics capture some common and some distinct phenotypic aspects of lung function; glycerophospholipid, linoleic acid and pyrimidine metabolism were common to all three characteristics. The corresponding metabolomic profiles showed moderate but robust discriminatory ability. CONCLUSIONS: The results confirm the existence of an asthma severity metabolome. However, differences in the metabolomic profiles of the three lung function characteristics studied, suggest that refinement of both phenotype classification and metabolite selection should be a priority as the field of asthma metabolomics progresses.