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.

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.

Functional Respiratory Evaluation in the COVID-19 Era: The Role of Pulmonary Function Test Laboratories.

The pandemic character of coronavirus disease-19 (COVID-19) requires strategy changes designed to guarantee the safety of patients and health-care professionals. We are greatly concerned by the limitations in the operation of pulmonary function test (PFT) laboratories, since there is a high risk of disease progression in patients with chronic pulmonary diseases, and we are now faced by the influx of a new group of individuals in the recovery phase of post-COVID-19-syndrome that requires evaluation and follow-up of their respiratory function. To reestablish the operation of PFT laboratories limiting the risk of cross-contamination, we herein present the consensus reached by a group of experts in respiratory physiology, most of whom work in PFT laboratories in several Latin American countries, on the applicable recommendations for severe acute respiratory syndrome coronavirus 2 pneumonia survivors when undergoing PFT. We present the safety and hygiene measures that must be adopted in laboratories or centers where PFT is conducted in adults and/or children. These recommendations answer the following questions: which PFT is most recommended in subjects that have recovered from COVID-19; what quality control and safety measures should PFT laboratories implement during this pandemic? And how should we approach non-COVID-19 patients requiring PFT?

Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

CONTROVERSIES AND LIMITATIONS IN THE DIAGNOSIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE.

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. While the cut-off point to define airflow obstruction has been controversial, it is widely accepted that the spirometry test is vital, as well as performing it after using a bronchodilator. The 6-second spirometry and the forced expiratory volume in 1 second/forced expiratory volume in 6 seconds (FEV1/FEV6) have demonstrated validity for defining obstruction, and it would be advisable to incorporate them in the definitions of obstruction. Another relevant issue is that spirometry with borderline obstruction can vary over time, changing to above or below the cut-off point. Thus, surveillance should be considered over time, repeating the spirometry to have a greater certainty in the diagnosis. The objective of this article was to conduct an in-depth review of the controversies in the diagnosis of COPD. During the past years, COPD definition has been updated in different times; however, it is now considered more as a complex syndrome with systemic participation, requiring a multidimensional assessment, and not only a spirometry.

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

[Prevalence of sleep symptoms and risk of obstructive sleep apnea in Mexico.] / Prevalencia de síntomas de sueño y riesgo de apnea obstructiva del sueño en México.

OBJECTIVE: To estimate the prevalence of sleep related symptoms (SRS) in Mexico, and their distribution by region, urbanization and gender. MATERIALS AND METHODS: Cross-sectional study using a national probabilistic sample among adults over 20 years old. We applied the Berlin questionnaire for sleep apnea risk (OSA) and questions on sleep duration, insomnia and sedative use. RESULTS: The most frequent SRS were snoring 48.5% and difficulty falling asleep 36.9%. High risk for OSA was found in 27.3% of adults, increases with BMI (OR=1.1), age (OR=1.03) and urban residence (OR=1.37). Insomnia was in 18.8% with female predominance (OR=1.91). Average sleep time was 7.6 ±3 hours; 28.4% of adults sleep <7 h/night. CONCLUSIONS: SRS are highly prevalent. One in four Mexican adults have an elevated risk for OSA. Their detection and treatment could minimize detrimental health outcomes for them.

OBJETIVO: Estimar la prevalencia nacional de síntomas asociados con el sueño (SAS) en México, y su distribución por región, localidad y sexo. MATERIAL Y MÉTODOS: Estudio transversal con muestreo probabilístico, representativo a nivel nacional en adultos mayores de 20 años. Se aplicó un cuestionario sobre duración de sueño, insomnio, uso de hipnóticos y riesgo de síndrome de apnea obstructiva del sueño (SAOS). RESULTADOS: Los SAS más frecuentes fueron ronquido (48.5%) y dificultad para dormir (36.9%). Se identificó riesgo elevado de SAOS en 27.3% de los adultos, y se incrementa por índice de masa corporal (RM=1.1), edad (RM=1.03) y habitar zona urbana (RM=1.37). Se reportó insomnio en 18.8% de los participantes, que predomina en mujeres (RM=1.88). La duración promedio de sueño fue de 7.6 ± 3 horas; 28.4% de los adultos duermen <7 horas/ noche. CONCLUSIONES: Existe una elevada prevalencia de SAS. Uno de cada cuatro adultos mexicanos tiene elevada probabilidad de padecer SAOS. La detección y tratamiento de SAS pudieran minimizar los efectos deletéreos en la salud.

Small airway dysfunction in chronic hypersensitivity pneumonitis.

BACKGROUND AND OBJECTIVE: Lung biopsies from patients with hypersensitivity pneumonitis (HP) have demonstrated small airway (SA) involvement, but there is no information concerning SA function in HP, and it is unknown whether pharmacological treatment could modify its function. SA function in patients with chronic HP using ultrasonic pneumography (UPG) and impulse oscillometry (IOS) was explored. We also compared initial results with those obtained after 4 weeks of standardized treatment with azathioprine and prednisone. METHODS: The study group consisted of adults with recent diagnoses of HP. All patients completed UPG, IOS, spirometry, body plethysmography, single-breath carbon monoxide diffusing capacity (DLCO ) and the 6-min walk test (6MWT). The fraction of exhaled nitric oxide (FENO ) was obtained to assess eosinophilic airway inflammation. Measurements were taken at diagnosis and after 4 weeks of treatment. RESULTS: A total of 20 consecutive patients (16 women) with chronic HP participated in the study. Median age was 50 years (interquartile range (IQR): 42-54). At diagnosis, the UPG phase 3 slope was abnormally high, consistent with maldistribution of ventilation. For IOS, all patients had low reactance at 5 Hz (X5) and elevated reactance area (AX) reflecting low compliance, and only eight (40%) patients had elevated R5 (resistance at 5 Hz (total)) and R5-20 (resistance at 5 Hz-resistance at 20 Hz (peripheral)) attributed to SA resistance. In contrast, FENO parameters were within normal limits. After treatment, forced vital capacity (FVC), the 6-min walk distance and the distribution of ventilation showed significant improvement, although DLCO did not. CONCLUSION: Patients with chronic HP have SA abnormalities that are partially revealed by the UPG and IOS tests. Lung volumes, but not gas exchange, improved after treatment with azathioprine and prednisone.

Variability of FeNO in healthy subjects at 2240 meters above sea level.

Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. Altitude above sea level can affect measurements of this index, but there is only limited information regarding the diurnal variation (ante meridiem vs. post meridiem) and reproducibility of FeNO on consecutive days at moderate altitudes. To evaluate the diurnal variability of FeNO and assess its reproducibility over five consecutive days in healthy individuals living at 2240 m, and to compare the FeNO readings taken with two different analyzers. Healthy non-smoking adults were measured using NIOX MINO(®) or NOA 280i(®) devices. One group (n = 10) had readings taken morning and afternoon for five consecutive days with the NIOX MINO(®) equipment; while the second group (n = 17) was measured on only one morning but by both the electrochemical analyzer (NIOX MINO(®)) and the chemiluminescence method (NOA 280i(®)). The study group consisted of 27 subjects aged 28.7 ± 6 years. Morning and afternoon FeNO measurements were 15.2 ± 7.5 ppb and 15.2 ± 7.9 ppb (p = 0.9), respectively. The coefficient of variation (CV) of these measurements (a.m. vs. p.m.) was 10.7 %, and the coefficient of repeatability (CR), 4.2 ppb. The concordance correlation coefficient (CCC) between the two measures (morning vs. afternoon) was 0.91. The CV and CR of the five morning readings were 15.4 % and 4.3 ppb, respectively; while those of the five afternoon measures were 13.6 % and 3.5 ppb, respectively. The CCC between the NIOX MINO(®) equipment and the NOA-280i(®) device was 0.8, with 95 % limits of agreement of -8.35 to 0.29 ppb. In adults living at 2240 m above sea level, FeNO measurements show minimal diurnal variation, and readings are reproducible (<15 %) over a period of at least five consecutive days; however, the FeNO measurements obtained with the NIOX MINO(®) and NOA 280i(®) devices are not interchangeable due to the wide limits of agreement recorded.

Obstructive Sleep Apnea and Perinatal Risk.

Obstructive sleep apnea is characterized by total or partial interruptions of airflow during sleep, despite ongoing efforts to breathe. These pauses result from repeated upper airway obstructions that generate a systemic inflammatory condition with consequences for the endothelial function that increase the risk of cardiometabolic events. The prevalence of obstructive sleep apnea during pregnancy is greater than that observed in the general population and increases in the third trimester. Although limited, the information currently available supports the notion that obstructive sleep apnea is an independent, and potentially modifiable, risk factor for maternal and perinatal morbidity and mortality. Experimental and prospective studies in humans have demonstrated an association between obstructive sleep apnea and low birth weight. Endothelial dysfunction may be the link that underlies the association of obstructive sleep apnea with high perinatal risk. The information reviewed herein suggests that treating obstructive sleep apnea with positive-pressure devices could be an effective strategy for decreasing perinatal morbidity and mortality.

Clinical Characteristics and Mortality of Influenza A H1N1 and Influenza-Like Illness in Mexico City in the 2013-2014 Winter Season.

BACKGROUND: The 2013-2014 influenza season in Mexico City was severe and mainly due to influenza A H1N1, as was the 2009 pandemic. OBJECTIVE: To describe features of the outbreak and to compare the characteristics of patients with and without viral identification. METHODS: We reviewed the medical charts of all individuals with influenza or influenza-like illness admitted to a referral hospital for respiratory diseases in Mexico City from January 2013 to March 2014, whether influenza virus was identified or not. RESULTS: We included 233 patients with influenza-like illness, 99 of whom had laboratory confirmed influenza; one-half of all patients required mechanical ventilation and 25% were admitted to the intensive care unit. Patients with confirmed influenza had a more severe disease than those without confirmation. A total of 52 (22.3%) patients died in hospital; survival was greater among patients hospitalized in the intensive care unit compared with those who remained in regular wards. CONCLUSIONS: Influenza A H1N1 continues to cause significant outbreaks in Mexico City. Patients with influenza-like illness had a similar clinical course regardless of laboratory confirmation of influenza, suggesting that their illness likely belonged to the same outbreak. Mechanical ventilation in regular hospital wards may be lifesaving, although the outcome is worse than at an intensive care unit.

Cardiorespiratory and sensory responses to exercise in well-controlled asthmatics.

OBJECTIVES: The purpose of this study was to evaluate detailed ventilatory, cardiovascular and sensory responses to cycle exercise in sedentary patients with well-controlled asthma and healthy controls. METHODS: Subjects included sedentary patients meeting criteria for well-controlled asthma (n = 14), and healthy age- and activity-matched controls (n = 14). Visit 1 included screening for eligibility, medical history, anthropometrics, physical activity assessment, and pre- and post-bronchodilator spirometry. Visit 2 included spirometry and a symptom limited incremental cycle exercise test. Detailed ventilatory, cardiovascular and sensory responses were measured at rest and throughout exercise. RESULTS: Asthmatics and controls were well matched for age, body mass index and physical activity levels. Baseline forced expiratory volume in 1 second (FEV(1)) was similar between asthmatics and controls (98 ± 10 versus 95 ± 9% predicted, respectively, p > 0.05). No significant differences were observed between asthmatics and controls for maximal oxygen uptake (31.8 ± 5.6 versus 30.6 ± 5.9 ml/kg/min, respectively, p > 0.05) and power output (134 ± 35 versus 144 ± 32 W, respectively, p > 0.05). Minute ventilation (V(E)) relative to maximum voluntary ventilation (V(E)/MVV) was similar between groups at maximal exercise with no subjects showing evidence of ventilatory limitation. Asthmatics and controls achieved similar age-predicted maximum heart rates (92 ± 7 versus 93 ± 8% predicted, respectively, p > 0.05). Ratings of perceived breathing discomfort and leg fatigue were not different between groups throughout exercise. CONCLUSIONS: The results of this study indicate that sedentary patients with well-controlled asthma have preserved sensory and cardiorespiratory responses to exercise with no evidence of exercise impairment or ventilatory limitation.

Functional respiratory assessment in interstitial lung disease.

Interstitial lung diseases are a heterogeneous group of disorders that affect, to a greater or lesser degree, the alveolus, peripheral airway, and septal interstitium. Functional assessment in patients suspected of having an interstitial lung disease has implications for diagnosis and makes it possible to objectively analyze both response to treatment and prognosis. Recently the clinical value of lung-diffusing capacity and the six-minute walking test has been confirmed, and these are now important additions to the traditional assessment of lung function that is based on spirometry. Here we review the state-of-the-art methods for the assessment of patients with interstitial lung disease.

Diagnostic Value of the Morphometric Model and Adjusted Neck Circumference in Adults with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obstructive sleep apnea syndrome is a major public health problem. The morphometric model and the Sleep Apnea Clinical Score are widely used to evaluate adults; however, neither of these tools has been validated in a Mexican population. OBJECTIVE: To determine the diagnostic value of the morphometric model and the Sleep Apnea Clinical Score and compare them with conventional clinical instruments. METHODS: A total of 97 individuals were recruited prospectively. Initial screening excluded 36, of whom nine were subjects without apnea; the remaining 52 were consecutive patients with obstructive sleep apnea syndrome diagnosed by nocturnal polysomnography. Diagnostic values of each test were calculated. RESULTS: Obstructive sleep apnea syndrome patients had significantly higher scores with both instruments than controls: morphometric model: 61.3 (95% CI: 45.5-75.3) vs. 41.0 (95% CI: 35.6-45.6); Sleep Apnea Clinical Score: 45.3 (95% CI: 39.5-40.3) vs. 36 (95% CI: 34.0-36.5), respectively. For severe cases, the best cutoff point for morphometric model was 46, with a sensitivity of 81% (95% CI: 62.5-92.6) and specificity of 46.7% (95% CI: 66.4-100), while for Sleep Apnea Clinical Score it was > 48, with a sensitivity of 61% (95% CI: 46.1-74.2) and specificity of 80.4% (95% CI: 66-90.6). CONCLUSIONS: A morphometric model value of ≥ 46 or an adjusted neck circumference (Sleep Apnea Clinical Score) > 48 were adequate for diagnosing obstructive sleep apnea syndrome.

Altitude Above Sea Level and Body Mass Index as Determinants of Oxygen Saturation in Children: The SON@ Study.

BACKGROUND: Altitude above sea level and body mass index are well-recognized determinants of oxygen saturation in adult populations; however, the contribution of these factors to oxygen saturation in children is less clear. OBJECTIVE: To explore the contribution of altitude above sea level and body mass index to oxygen saturation in children. METHODS: A multi-center, cross-sectional study conducted in nine cities in Mexico. Parents signed informed consent forms and completed a health status questionnaire. Height, weight, and pulse oximetry were recorded. RESULTS: We studied 2,200 subjects (52% girls) aged 8.7 ± 3.0 years. Mean body mass index, z-body mass index, and oxygen saturation were 18.1 ± 3.6 kg·m-2, 0.58 ± 1.3, and 95.5 ± 2.4%, respectively. By multiple regression analysis, altitude proved to be the main predictor of oxygen saturation, with non-significant contributions of age, gender, and body mass index. According to quantile regression, the median estimate of oxygen saturation was 98.7 minus 1.7% per km of altitude above sea level, and the oxygen saturation fifth percentile 97.4 minus 2.7% per km of altitude. CONCLUSIONS: Altitude was the main determinant of oxygen saturation, which on average decreased 1.7% per km of elevation from a percentage of 98.7 at sea level. In contrast with adults, this study in children found no association between oxygen saturation and obesity or age.

The Tim3-galectin 9 pathway induces antibacterial activity in human macrophages infected with Mycobacterium tuberculosis.

T cell Ig and mucin domain 3 (Tim3) is an inhibitory molecule involved in immune tolerance, autoimmune responses, and antiviral immune evasion. However, we recently demonstrated that Tim3 and Galectin-9 (Gal9) interaction induces a program of macrophage activation that results in killing of Mycobacterium tuberculosis in the mouse model of infection. In this study, we sought to determine whether the Tim3-Gal9 pathway plays a similar role in human pulmonary TB. We identified that pulmonary TB patients have reduced expression of Tim3 on CD14(+) monocytes in vivo. By blocking Tim3 and Gal9 interaction in vitro, we show that these molecules contribute to the control of intracellular bacterial replication in human macrophages. The antimicrobial effect was partially dependent on the production of IL-1ß. Our results establish that Tim3-Gal9 interaction activates human M. tuberculosis -infected macrophages and leads to the control of bacterial growth through the production of the proinflammatory cytokine IL-1ß. Data presented in this study suggest that one of the potential pathways activated by Tim3/Gal9 is the secretion of IL-1ß, which plays a crucial role in antimicrobial immunity by modulating innate inflammatory networks.

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.

[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.

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.