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.

Effect of Altitude on Respiratory Functional Status in COVID-19 Survivors: Results from a Latin American Cohort-FIRCOV.

Laura Gochicoa-Rangel, Santiago C. Arce, Carlos Aguirre-Franco, Wilmer Madrid-Mejía, Mónica Gutiérrez-Clavería, Lorena Noriega-Aguirre, Patricia Schonffeldt-Guerrero, Agustín Acuña-Izcaray, Arturo Cortés-Telles, Luisa Martínez-Valdeavellano, Federico Isaac Hernández-Rocha, Omar Ceballos-Zúñiga, Rodrigo Del Rio Hidalgo, Sonia Sánchez, Erika Meneses-Tamayo, and Iván Chérrez-Ojeda; and on Behalf of the Respiratory Physiology Project in COVID-19 (FIRCOV). Effect of altitude on respiratory functional status in COVID-19 survivors: results from a Latin American Cohort-FIRCOV. High Alt Med Biol 24:37-48, 2023. Persistent symptoms and lung function abnormalities are common in COVID-19 survivors. Objectives: To determine the effect of altitude and other independent variables on respiratory function in COVID-19 survivors. Methods: Analytical, observational, cross-sectional cohort study done at 13 medical centers in Latin America located at different altitudes above sea level. COVID-19 survivors were invited to perform pulmonary function tests at least 3 weeks after diagnosis. Results: 1,368 participants (59% male) had mild (20%), moderate (59%), and severe (21%) disease. Restriction by spirometry was noted in 32%; diffusing capacity of the lung for carbon monoxide (DLCO) was low in 43.7%; and 22.2% walked less meters during the 6-minute walk test (6-MWT). In multiple linear regression models, higher altitude was associated with better spirometry, DLCO and 6-MWT, but lower oxygen saturation at rest and during exercise. Men were 3 times more likely to have restriction and 5.7 times more likely to have a low DLCO. Those who had required mechanical ventilation had lower DLCO and walked less during the 6-MWT. Conclusions: Men were more likely to have lower lung function than women, even after correcting for disease severity and other factors. Patients living at a higher altitude were more likely to have better spirometric patterns and walked farther but had lower DLCO and oxygen saturation.

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.

Quality of Pulmonary Function Tests in Participants with Down Syndrome.

INTRODUCTION: People with Down syndrome (DS) have high respiratory morbidity, evaluating their respiratory health with standardized, objective tests is desirable. Thus, the objective of this study was to evaluate the technical quality of Pulmonary Function Tests (PFTs) to determine which ones are most suitable for this population. METHODS: Participants included children, teenagers and adults with DS, 5 years of age or older (n=302). The technical quality of the impulse oscillometry system (IOS), forced spirometry, lung-diffusing capacity for carbon monoxide (DLCO), and 6-min walk test (6MWT) were analyzed by age group. Capnography and pulse oximetry were included in the study. Technical quality was determined on the basis of current international PFTs standards. RESULTS: Fifty-one percent of participants were males. A total of 184 participants (71%) who completed the IOS fulfilled the quality criteria, while 210 (70%) completed the 6MWT. Performance on forced spirometry and DLCO was poor. All pulse oximetries and 96% percent heart rates obtained had good quality, but exhaled carbon dioxide (PetCO2) and respiratory rate (RR) showed deficient repeatability. CONCLUSIONS: IOS appears to be the most reliable instrument for evaluating lung mechanics in individuals with DS.

Inspiratory Capacity and Vital Capacity of Healthy Subjects 9-81 Years of Age at Moderate-High Altitude.

BACKGROUND: Measurements of inspiratory capacity (IC) and vital capacity (VC) are used to recognize dynamic hyperinflation, but appropriate reference values are required to achieve accurate clinical interpretations. Altitude above sea level is a potential determining factor for lung volumes, including IC and VC. OBJECTIVE: To describe IC and VC for healthy people who live in Mexico City at an altitude of 2,240 m above sea level. METHODS: Healthy subjects ages 9-81 y completed slow spirometry by following 2005 American Thoracic Society/European Respiratory Society standards. Once associations were explored, linear regression models were constructed and values were compared with those from previously published equations. RESULTS: A total of 441 healthy subjects (55.1% women) participated. The mean age was 32 y (minimum age, 9 y; maximum age, 81 y). IC and VC measurements were associated with sex, age, height, and weight. An accelerated increase in IC and VC was evident from 9 to 20 y of age, followed by a gradual decrease in both sexes. In general, IC was higher in our population than predicted by previously published reference equations. CONCLUSIONS: IC in healthy people at 2,240 m above sea level was higher than that of previous reports about European and Latin-American subjects of the same height, sex, and age who were at sea level. The present study provided robust reference values for persons who lived at a moderate altitude.

Diffusing Capacity of the Lung for Carbon Monoxide in Mexican/Latino Children. Quality Control and Reference Values.

RATIONALE: Single-breath diffusing capacity of the lung for carbon monoxide (DlCOsb) values are used to evaluate gas exchange; however, the quality of maneuvers performed by children has not been evaluated, and reference values for young people living at moderate altitudes are not well established. OBJECTIVES: Our objectives were 1) to determine whether DlCOsb maneuvers performed by a pediatric population would meet 2017 European Respiratory Society/American Thoracic Society (ERS/ATS) quality control standards; and 2) to report normal DlCOsb values for Mexican/Latino children and adolescents living at moderate altitudes. METHODS: This study involved healthy young people 4-20 years of age from the metropolitan area of Mexico City (2,240 m above sea level) who were recruited in schools from July 2014 to August 2017. DlCOsb testing was performed according to the 2005 ATS/ERS standards, and the quality control of each maneuver was analyzed according to the 2017 ERS/ATS standards. We constructed models for DlCOsb with linear and quadratic terms for weight, height, and age as independent variables using shrinkage statistics, variance inflation factors, the Akaike information criterion, and R2 to compare the results of different models. RESULTS: Results were obtained for 420 individuals (53% boys) with a mean age of 11.7 ± 4.5 standard deviation (SD) years; 47% of maneuvers from children age 4-6 years were grade A (13% grade B), and 90% of those in children older than 13 years were grade A or B. Forty-six percent of the subjects had a DlCOsb repeatability of <1 ml/min/mm Hg. The mean DlCOsb was higher for boys than for girls (32.4 ± 13.6 [SD] vs. 24.1 ± 7.5 ml/min/mm Hg, respectively). The reference equation for boys was DlCOsb = exp(1.63469 + [0.03251 × age] + [0.00846 × height] + [0.00304 × weight]), R2 = 0.87; for girls, the best equation was DlCOsb = exp(1.56516 + [0.0193 × age] + [0.00893 × height] + [0.00273 × weight]), R2 = 0.75. The single-breath transfer coefficient of the lung for carbon monoxide remained constant with age and height, with a lower limit of normal of 6.5 ml/min/mm Hg/L in boys and 5.4 ml/min/mm Hg/L in girls. Measured DlCOsb was higher than predicted by other authors (P < 0.001 by paired t test). CONCLUSIONS: Individuals 4-20 years of age can complete high-quality DlCOsb tests. Children and adolescents living at 2,240 m have higher DlCOsb values than those living at sea level. Reference equations for DlCOsb obtained at sea level are poor predictors of the values measured at moderate altitude.

Validating Reference Equations for Impulse Oscillometry in Healthy Mexican Children.

BACKGROUND: The impulse oscillometry system (IOS) measures the impedance (Z) of the respiratory system, but proper interpretation of its results requires adequate reference values. The objectives of this work were: (1) to validate the reference equations for the IOS published previously by our group and (2) to compare the adjustment of new available reference equations for the IOS from different countries in a sample of healthy children. METHODS: Subjects were healthy 4-15-y-old children from the metropolitan area of Mexico City, who performed an IOS test. The functional IOS parameters obtained were compared with the predicted values from 12 reference equations determined in studies of different ethnic groups. The validation methods applied were: analysis of the differences between measured and predicted values for each reference equation; correlation and concordance coefficients; adjustment by Z-score values; percentage of predicted value; and the percentage of patients below the lower limit of normality or above the upper limit of normality. RESULTS: Of the 224 participants, 117 (52.3%) were girls, and the mean age was 8.6 ± 2.3 y. The equations that showed the best adjustment for the different parameters were those from the studies by Nowowiejska et al (2008) and Gochicoa et al (2015). The equations proposed by Frei et al (2005), Hellinckx et al (1998), Kalhoff et al (2011), Klug and Bisgaard (1998), de Assumpção et al (2016), and Dencker et al (2006) overestimated the airway resistance of the children in our sample, whereas the equation of Amra et al (2008) underestimated it. In the analysis of the lower and upper limits of normality, Gochicoa et al equation was the closest, since 5% of subjects were below or above percentiles 5 and 95, respectively. The study found that, in general, all of the equations showed greater error at the extremes of the age distribution. CONCLUSIONS: Because of the robust adjustment of the present study reference equations for the IOS, it can be recommended for both clinical and research purposes in our population. The differential adjustment of other equations underlines the need to obtain local reference values.