Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross-sectional study.

Pulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z-score or percent predicted. Ninety-six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in boys were associated with zR5-R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM-CSF. This endogenous influence is a novel concept that warrants in-depth characterization.

Reference equations using segmented regressions for impulse oscillometry in healthy subjects aged 2.7-90 years.

Background: Published reference equations for impulse oscillometry (IOS) usually encompass a specific age group but not the entire lifespan. This may lead to discordant predicted values when two or more non-coincident equations can be applied to the same person, or when a person moves from one equation to the next non-convergent equation as he or she gets older. Thus, our aim was to provide a single reference equation for each IOS variable that could be applied from infancy to old age. Methods: This was an ambispective cross-sectional study in healthy nonsmokers, most of whom lived in Mexico City, who underwent IOS according to international standards. A multivariate piecewise linear regression, also known as segmented regression, was used to obtain reference equations for each IOS variable. Results: In a population of 830 subjects (54.0% female) aged 2.7 to 90 years (54.8% children ≤12 years), segmented regression estimated two breakpoints for age in almost all IOS variables, except for R5-R20 in which only one breakpoint was detected. With this approach, multivariate regressions including sex, age, height and body mass index as independent variables were constructed, and coefficients for calculating predicted value, lower and upper limits of normal, percentage of predicted and z-score were obtained. Conclusions: Our study provides IOS reference equations that include the major determinants of lung function, i.e. sex, age, height and body mass index, that can be easily implemented for subjects of almost any age.

[Small airway: from definition to treatment]. / Vía aérea pequeña: de la definición al tratamiento.

The small airway, present since the origins of humanity and described barely a century ago, has recently been discovered as the anatomical site where inflammation begins in some obstructive lung diseases, such as asthma and Chronic Obstructive Pulmonary Disease (COPD), per se. Small airway dysfuction was identified in up to 91% of asthmatic patients and in a large proportion of COPD patients. In subjects without pathology, small airway represent 98.8% (approximately 4500 ml) of the total lung volume, contributing only between 10-25% of the total lung resistance; however, in subjects with obstruction, it can represent up to 90% of the total resistance. Despite this, its morphological and functional characteristics allow its dysfunction to remain undetected by conventional diagnostic methods, such as spirometry. Hence the importance of this review, which offers an overview of the tools available to assess small airway dysfunction and the possible therapies that act in this silent zone.

La vía aérea pequeña, presente desde los orígenes de la humanidad y descrita hace apenas un siglo, se ha descubierto recientemente como el sitio anatómico donde inicia la inflamación provocada por algunas enfermedades pulmonares obstructivas: asma y enfermedad pulmonar obstructiva crónica (EPOC), per se. Se ha identificado disfunción de la vía aérea pequeña en el 91% de los pacientes asmáticos y en una gran proporción de quienes padecen EPOC. En los pacientes sin enfermedad, la vía aérea pequeña representa el 98.8% (4500 mL) del volumen pulmonar total, y solo aporta del 10 al 25% de la resistencia pulmonar total; sin embargo, en sujetos con obstrucción puede suponer el 90% de la resistencia total. A pesar de esto, sus características morfológicas y funcionales permiten que la disfunción pase inadvertida por métodos diagnósticos convencionales, por ejemplo la espirometría. Con base en lo anterior, el objetivo de este estudio fue revisar el panorama general de los métodos disponibles para evaluar la vía aérea pequeña y los posibles tratamientos asociados con esta zona silente.

Maximal inspiratory and expiratory flow at moderate altitude: a study of a Latin American population.

BACKGROUND: Peak inspiratory and expiratory flows (PIF, PEF) are parameters used to evaluate the mechanics of the respiratory system. These parameters can vary based on whether they are measured using mechanical devices vs. spirometry and based on the barometric pressure at which the measurements are obtained. Our objectives were (1) to report the normal values and variability of PEF and PIF of a Latin American population living at a moderate altitude (2240 m above sea level), (2) to analyze the adjustment of reference values obtained at sea level with those obtained in healthy subjects living at a moderate altitude, and (3) to assess the correlation between PEF obtained by spirometry (PEFs) and PEF obtained by mechanical devices (PEFm). METHODS: In this prospective and transversal study, men and women with good respiratory health aged between 2.8 and 68 years old were invited to participate. Randomly, they underwent spirometry (to measure PEFs and PIFs) and mechanical flowmetry (to measure PEFm). RESULTS: A total of 314 subjects participated, with an average age of 24.3 ± 16.4 years; 59% were Women. The main determinants for the reference equations were age, weight, height and sex at birth. The agreement of the PEFm, PEFs and PIFs values was inconsistent with that reported by other authors, even at the same barometric pressure. The association between PEFm and PEFs was r = 0.91 (p < 0.001), and the correlation coefficient of concordance was 0.84. CONCLUSIONS: The PEFm, PEFs, and PIFs measurements in individuals living at moderate altitudes are different from those found by other authors in cities with different barometric pressures and ethnicities.

Offline exhaled nitric oxide in children: chemiluminescence vs. electrochemical devices / Óxido nítrico exhalado «fuera de línea¼ en niños: comparación entre equipos de quimioluminiscencia y electroquímicos

Abstract Background: Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation that has been used in children, using the "offline" technique. To the extent of our knowledge, no article reported in literature compares the concordance and correlation between the two different technologies used to measure eNO at tidal volume offline. This study aimed to report the concordance and correlation of the eNO measured "offline" at tidal volume, using chemioluminiscence (cl) vs electrochemical devices (eq). Methods: A cross-sectional, observational, and prospective study was conducted in the National Institute of Respiratory Diseases (Instituto Nacional de Enfermedades Respiratorias), Mexico City. Healthy children and those with a lung disease between 1 and 11 years of age were included. The exhaled air sample at tidal volume was obtained by attaching a mask connected to a Mylar® bag. Results: We studied 36 children. The mean ± standard deviation (SD) age of the study population was 6 ± 2.6 years; 25% of the subjects included were healthy, and the rest had a lung disease. The concordance correlation coefficient between the two measuring devices was 0.98 (p < 0.001), with a mean difference of 1.46 ± 3.5 ppb and 95% limits of agreement from -5.3 ppb to 8.3 ppb. The linear regression model equation for the estimation of eNO was eNOcl = (eNOeq·1.0718) - 0.1343 (r2 = 0.97). Conclusions: The measurement of eNO at tidal volume by the offline method can be analyzed by electrochemical devices, and the results are interchangeable with those analyzed by chemiluminescence technology.

Resumen Introducción: El óxido nítrico exhalado (eNO) es un marcador no invasivo de inflamación de la vía aérea que se ha utilizado en niños mediante técnica «fuera de línea¼. Por lo que sabemos, en la literatura no existen reportes que comparen la concordancia y la correlación entre dos técnicas diferentes a volumen corriente. El objetivo de este trabajo es informar la concordancia y la correlación del eNO obtenido por la técnica fuera de línea a volumen corriente en los equipos de quimioluminiscencia (cl) y electroquímico (eq). Métodos: Se realizó un estudio transversal, observacional y prospectivo en el Instituto Nacional de Enfermedades Respiratorias, en Ciudad de México. Se incluyeron niños sanos y con enfermedad pulmonar de 1-11 años de edad. La muestra de aire exhalado se obtuvo a volumen corriente mediante una máscara con conexión a una bolsa de Mylar®. Resultados: Se estudiaron 36 niños. La edad promedio con su desviación estándar de la población de estudio fue de 6 ± 2.6 años. El 25% de los sujetos incluidos estaban sanos y el resto tenían alguna enfermedad pulmonar. El coeficiente de correlación de concordancia entre los dos equipos fue de 0.98 (p < 0.001), con una diferencia media de 1.46 ± 3.5 ppb y unos límites de concordancia del 95% de −5.3 a 8.3 ppb. La ecuación del modelo de regresión lineal del eNO fue eNOcl = (eNOeq·1,0718) − 0.1343 (r2 = 0.97). Conclusiones: La medición del eNO por el método fuera de línea a volumen corriente puede analizarse en dispositivos electroquímicos. Los resultados son intercambiables con los de quimioluminiscencia.

Gas Exchange Impairment During COVID-19 Recovery.

BACKGROUND: Persistent impairment of pulmonary function and exercise capacity has been known to last for months or even years in the survivors who recovered from other coronavirus pneumonia. Some reports showed that subjects with coronavirus disease 2019 pneumonia after being discharged could have several sequelae, but there are few studies on gas exchange and exercise capacity complications in these subjects. AIMS: To describe residual gas exchange abnormalities during recovery from coronavirus disease 2019 pneumonia. METHODS: In an observational study, ∼90 d after onset of disease, we scheduled almost 200 subjects for an out-patient visit with pulmonary function testing and computed tomography of the lungs. Lung mechanics by using body plethysmography, gas exchange with diffusing lung capacity for carbon monoxide determined by the single-breath technique (DLCOsb) and diffusing lung capacity for nitric oxide determined by the single-breath technique (DLNOsb), and exercise ability by using the 6-min walk test (6MWT) were measured in the subjects. The results were compared between those who required invasive mechanical ventilation and those who did not. RESULTS: A total of 171 subjects were included, the majority (96%) had signs of residual pneumonia (such as an excess of high attenuation areas) on computed tomography of the lungs. The DLCOSB results were below the lower limit of the normal range in 29.2% of the subjects; during the 6MWT, 67% experienced oxygen desaturation ([Formula: see text]) > 4%; and, in 81 (47%), the dropped below 88%. Subjects who required invasive mechanical ventilation (49.7%) were more likely to have lower lung volumes, more gas exchange abnormality, less exercise capacity and more radiologic abnormality. CONCLUSIONS: Subjects who recovered from severe COVID-19 pneumonia continued to have abnormal lung function and abnormal radiologic findings.

Offline exhaled nitric oxide in children: chemiluminescence vs. electrochemical devices.

Background: Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation that has been used in children, using the "offline" technique. To the extent of our knowledge, no article reported in literature compares the concordance and correlation between the two different technologies used to measure eNO at tidal volume offline. This study aimed to report the concordance and correlation of the eNO measured "offline" at tidal volume, using chemioluminiscence (cl) vs electrochemical devices (eq). Methods: A cross-sectional, observational, and prospective study was conducted in the National Institute of Respiratory Diseases (Instituto Nacional de Enfermedades Respiratorias), Mexico City. Healthy children and those with a lung disease between 1 and 11 years of age were included. The exhaled air sample at tidal volume was obtained by attaching a mask connected to a Mylar® bag. Results: We studied 36 children. The mean ± standard deviation (SD) age of the study population was 6 ± 2.6 years; 25% of the subjects included were healthy, and the rest had a lung disease. The concordance correlation coefficient between the two measuring devices was 0.98 (p < 0.001), with a mean difference of 1.46 ± 3.5 ppb and 95% limits of agreement from -5.3 ppb to 8.3 ppb. The linear regression model equation for the estimation of eNO was eNOcl = (eNOeq·1.0718) - 0.1343 (r2 = 0.97). Conclusions: The measurement of eNO at tidal volume by the offline method can be analyzed by electrochemical devices, and the results are interchangeable with those analyzed by chemiluminescence technology.

Introducción: El óxido nítrico exhalado (eNO) es un marcador no invasivo de inflamación de la vía aérea que se ha utilizado en niños mediante técnica «fuera de línea¼. Por lo que sabemos, en la literatura no existen reportes que comparen la concordancia y la correlación entre dos técnicas diferentes a volumen corriente. El objetivo de este trabajo es informar la concordancia y la correlación del eNO obtenido por la técnica fuera de línea a volumen corriente en los equipos de quimioluminiscencia (cl) y electroquímico (eq). Métodos: Se realizó un estudio transversal, observacional y prospectivo en el Instituto Nacional de Enfermedades Respiratorias, en Ciudad de México. Se incluyeron niños sanos y con enfermedad pulmonar de 1-11 años de edad. La muestra de aire exhalado se obtuvo a volumen corriente mediante una máscara con conexión a una bolsa de Mylar®. Resultados: Se estudiaron 36 niños. La edad promedio con su desviación estándar de la población de estudio fue de 6 ± 2.6 años. El 25% de los sujetos incluidos estaban sanos y el resto tenían alguna enfermedad pulmonar. El coeficiente de correlación de concordancia entre los dos equipos fue de 0.98 (p < 0.001), con una diferencia media de 1.46 ± 3.5 ppb y unos límites de concordancia del 95% de −5.3 a 8.3 ppb. La ecuación del modelo de regresión lineal del eNO fue eNOcl = (eNOeq·1,0718) − 0.1343 (r2 = 0.97). Conclusiones: La medición del eNO por el método fuera de línea a volumen corriente puede analizarse en dispositivos electroquímicos. Los resultados son intercambiables con los de quimioluminiscencia.

Comparing Spirometric Reference Values From Childhood to Old Age Estimated by LMS and Linear Regression Models.

BACKGROUND: Proper reference values for lung function testing are essential for achieving adequate interpretations. The LMS procedure (lambda, mu, sigma) permits continuous analyses of entire populations avoiding gaps in the transition between childhood and adulthood. It also allows more precise calculations of average values, dispersion, and 5th percentiles, which are usually considered the lower limit of normality. The objective of this study was to compare our results fitted with the LMS method with standard multiple linear regression, and with those from international Global Lung Function Initiative (GLI) equations. METHODS: Data from 9835 healthy residents of the metropolitan area of Mexico City aged 8-80 years were compiled from several studies: EMPECE, PLATINO, adult Mexican workers and two unpublished studies. The LMS procedure and multiple linear regression models were fit to obtain reference equations using R software. RESULTS: Residuals from the LMS models had a median closer to zero, and smaller dispersion than those from the linear model, but differences although statistically significant were very small and of questionable practical relevance. For example, for females and ln(FEV1), median residual was -0.001 with p25 of -0.08 and p75 of 0.08 for LMS, compared with 0.004 (-0.08, 0.09) [p<0.05] for the linear model. Average spirometric values for a given height for our population, were higher than those predicted by the GLI study. CONCLUSION: Continuous reference equations for the Mexican population calculated using the LMS technique showed slightly better fit than linear regression models.

Salivary concentrations of cytokines and other analytes in healthy children.

BACKGROUND: Blood has been the usual biological fluid for measuring analytes, but there is mounting evidence that saliva may be also useful for detecting cytokines in a noninvasive way. Thus, in this study we aimed to determine concentration of cytokines and other analytes in saliva from a population of healthy children. METHODS: We collected un-stimulated whole saliva samples from clinically healthy children, and concentration of 17 cytokines and 12 other analytes were measured in supernatants. All values were adjusted by albumin content and were log-transformed before multivariate statistical analysis. RESULTS: We included 114 children (53.5% females) between 6.0 and 11.9 years old. The highest concentrations (medians, pg/µg albumin) were seen for visfatin (183.70) and adiponectin (162.26) and the lowest for IL-13 and IL-2 (~0.003). Albumin concentration was associated with age (rS = 0.39, p < 0.001). In the multivariate analysis, five analytes (C peptide, ghrelin, GLP-1, glucagon, leptin) inversely correlated with age and positively with height-for-age. Age was also positively associated with PAI-1, while height-for-age was also positively associated with insulin and visfatin. Finally, BMI-for-age had a positive correlation with GM-CSF and insulin. CONCLUSIONS: Herein, we provided concentration values for 29 analytes in saliva from healthy children that may be useful as preliminary reference framework in the clinical research setting.