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.

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.

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

Abstract 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.

Macrophage Exposure to Polycyclic Aromatic Hydrocarbons From Wood Smoke Reduces the Ability to Control Growth of Mycobacterium tuberculosis.

Use of solid fuels for cooking or home heating has been related to various diseases of the respiratory tract. Woodsmoke contains a mixture of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds. Inhalation of these materials induces local and systemic changes in the immune system which may impair critical cell defense mechanisms; however, few studies have investigated the early effects that PAH exposures have on immune cells as macrophages. The aim of this study was to analyze if the pre-exposure to PAHs derived from woodsmoke deteriorates macrophage ability to control the intracellular growth of Mycobacterium tuberculosis. By using an in vitro experimental model, we analyzed the phenotype and some metabolic changes on THP-1 and monocyte-derived macrophages. Our results demonstrated that exposure to PAHs leads to cell activation and deteriorates mitochondrial function of the macrophage thus facilitating growth of M. tuberculosis.

Longitudinal Evaluation of Lung Function in Patients With Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiation Therapy.

PURPOSE: In lung cancer patients, radiation therapy modifies lung architecture, resulting in functional deterioration, which worsens symptoms and reduces quality of life. METHODS AND MATERIALS: A multicenter, prospective, longitudinal study was conducted in a cohort of patients with locally advanced and oligometastatic non-small cell lung cancer treated with concurrent chemoradiation therapy (CCRT). A wide array of pulmonary function tests (forced spirometry, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity, fraction of exhaled nitric oxide, arterial blood gases, and 6-minute walk test) were used to evaluate lung function at baseline; after radiation therapy; and at 6, 12, 24, and 48 weeks after CCRT. Relative changes in test results (percentages) were estimated at the aforementioned intervals and compared with baseline results. RESULTS: Thirty-seven patients completed the follow-up and were included in the analysis. After CCRT, patients showed a maximum decline in lung volumes as follows: (1) 31% in forced expiratory volume in the first second after 24 weeks (P = .008), (2) 9.6% in forced vital capacity after 48 weeks (P = .04), and (3) 15.1% in total lung capacity after 48 weeks (P = .0015). Similarly, at 12 weeks after CCRT, patients showed a 21.8% decrease in carbon monoxide diffusing capacity (P = .002). Increases were found in total airway resistance (respiratory system resistance at 5 Hz), frequency dependence of resistance (change in respiratory system resistance at 5 Hz-respiratory system resistance at 20 Hz, P = .012), and reactance (P = .0003 for respiratory system reactance at 5 Hz and P = .001 for reactance area), which together indicate small-airway dysfunction. CONCLUSIONS: The longitudinal evaluation of lung function through pulmonary function tests detects CCRT-induced damage before the appearance of clinical symptoms associated with CCRT lung toxicity.

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.

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

Resumen: 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.

Abstract: 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.

Respiratory impedance in patients with Duchenne muscular dystrophy.

Impulse oscillometry (IOS) evaluates non-effort-dependent respiratory mechanics, and thus it may be useful to evaluate patients with Duchenne muscular dystrophy (DMD). OBJECTIVES: We aimed (1) to describe the behavior of IOS parameters in patients with DMD, and compare it to those from a control group; (2) to determine whether resistances and reactances differ in relation to the severity of DMD; and (3) to compare IOS parameters with spirometry and maximal inspiratory (MIP) and expiratory (MEP) pressures. METHODS: Children and adolescents (<20 years old) with biopsy-confirmed DMD and age-paired subjects were cross-sectionally evaluated. All results were transformed to z scores with respect to the healthy subjects (reference population). RESULTS: Anthropometric characteristics did not differ between the 31 patients and 69 controls included in the study. Compared with controls, patients with DMD had higher IOS resistances and lower reactances. As expected, FEV1 and FVC were lower in patients and always declined as age increased. By contrast, MIP and MEP were lower-than-normal in youngest patients, tended to improve around puberty initiation, and declined thereafter. In general, there was a poor correlation between IOS parameters and spirometric variables or respiratory pressures, excepting for X20 Hz, which had an inverse correlation with FEV1 . Interestingly, IOS resistances were higher in patients with less disability (lower Vignos score; better FVC), but tended to be normalized in advanced stages of the disease. CONCLUSION: This study showed that IOS is feasible in children and adolescents with DMD and yields information about respiratory function not achievable with the usual forced techniques. Pediatr Pulmonol. 2016;51:1072-1079. © 2016 Wiley Periodicals, Inc.

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.

Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients.

INTRODUCTION: T cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD-1) are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim-3 and PD-1 is induced after chronic antigen-specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim-3 with its ligand galectin-9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim-3 expression profile before and after six months of antiretroviral therapy and the impact of Tim-3 and PD-1 blocking on immunity against M. tuberculosis. MATERIALS AND METHODS: HIV+ patients naïve to anti-retroviral therapy (ART) were followed up for six months. Peripheral immune-cell phenotype (CD38/HLA-DR/galectin-9/Tim-3 and PD-1) was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array) by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis-infected macrophages were cultured with T cells in the presence or absence of Tim-3 and PD-1 blocking antibodies. Interleukin-1 beta treatment of infected macrophages was evaluated by enumerating colony-forming units. RESULTS: We showed that HIV+ patients had an increased expression of Tim-3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim-3 and PD-1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. CONCLUSIONS: In this study, we demonstrated that increased Tim-3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and the in vitro manipulation of the Tim-3 and PD-1 molecules restored the functionality of T cells and macrophages to restrict bacterial growth. Our results provide a novel immune strategy that may be implemented in the near future in order to improve the immune responses in HIV+ patients.

Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages.

Lipoarabinomannan (LAM) is a lipid virulence factor secreted by Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis. LAM can be measured in the urine or serum of tuberculosis patients (TB-patients). Circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to LAM in patients with active TB. We speculated that exposing monocytes to LAM could produce phenotypically and functionally immature macrophages. To test our hypothesis, human monocytes were stimulated with LAM (24-120 hours) and various readouts were measured. The study showed that when monocytes were exposed to LAM, the frequency of CD68(+), CD33(+), and CD86(+) macrophages decreased, suggesting that monocyte differentiation into mature macrophages was affected. Regarding functionality markers, TLR2(+) and TLR4(+) macrophages also decreased, but the percentage of MMR(+) expression did not change. LAM-exposed monocytes generated macrophages that were less efficient in producing proinflammatory cytokines such as TNF-α and IFN-γ; however, their phagocytic capacity was not modified. Taken together, these data indicate that LAM exposure influenced monocyte differentiation and produced poorly functional macrophages with a different phenotype. These results may help us understand how mycobacteria can limit the quality of the innate and adaptive immune responses.

Pre-exposure of Mycobacterium tuberculosis-infected macrophages to crystalline silica impairs control of bacterial growth by deregulating the balance between apoptosis and necrosis.

Inhalation of crystalline silica (CS) particles increases the risk of pulmonary tuberculosis; however, the precise mechanism through which CS exposure facilitates Mycobacterium tuberculosis (Mtb) infection is unclear. We speculate that macrophage exposure to CS deregulates the cell death pathways that could explain, at least in part, the association observed between exposure to CS and pulmonary tuberculosis. We therefore established an in vitro model in which macrophages were exposed to CS and then infected with Mtb. Expression of surface markers was analyzed by flow cytometry, JNK1/2, ASK1, caspase 9, P-p38, Bcl-2 and Mcl-1 were analyzed by Western blot, and cytokines by ELISA. Our results show that exposure to CS limits macrophage ability to control Mtb growth. Moreover, this exposure reduced the expression of TLR2, Bcl-2 and Mcl-1, but increased that of JNK1 and ASK1 molecules in the macrophages. Finally, when the pre-exposed macrophages were infected with Mtb, the concentrations of TNFα, IL-1ß and caspase-9 expression increased. This pro-inflammatory profile of the macrophage unbalanced the apoptosis/necrosis pathway. Taken together, these data suggest that macrophages exposed to CS are sensitized to cell death by MAPK kinase-dependent signaling pathway. Secretion of TNF-α and IL-1ß by Mtb-infected macrophages promotes necrosis, and this deregulation of cell death pathways may favor the release of viable bacilli, thus leading to the progression of tuberculosis.

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.

In vitro cytotoxicity of CD8+ T cells in multi-drug-resistant tuberculosis. A preliminary report.

BACKGROUND AND OBJECTIVE: Specific CD8+ T-cell cytotoxicity has been recognized as being involved in the elimination of drug-susceptible tuberculosis (DS-TB). Given that there is currently no information on the cytotoxic effector functions of CD8+ T cells in multi-drug-resistant tuberculosis (MDR-TB), our objective was to analyse the cytotoxic activity, both basal and stimulated, of CD8+ T cells from MDR-TB patients and compare it with that of DS-TB patients, as well as purified protein derivative (PPD)+ and PPD- subjects. METHODS: Cytotoxic activity of CD8+ T cells from MDR-TB patients, DS-TB patients, PPD+ and PPD- subjects was measured by a colorimetric assay, using H37Rv culture filtrate protein as the antigenic stimulus. RESULTS: Twenty-eight subjects were studied (7 MDR-TB patients, 7 DS-TB patients, 7 PPD+ subjects and 7 PPD- subjects). In the presence of the antigenic stimulus, the cytotoxic activity of CD8+ T cells from MDR-TB patients (% lysis) increased from 6.7% to 59.6% (P < 0.001). In DS-TB patients lysis increased from 3.2% to 22.5% (P < 0.001), whereas in PPD+ subjects it increased from 2.7% to 12.0% (P < 0.001) and in PPD- subjects from 1.3% to 3.2% (P < 0.001). Basal cytotoxic activity was significantly higher for MDR-TB patients than PPD+ and PPD- subjects (P = 0.003), but not compared with that for DS-TB patients (P = 0.05). Stimulated cytotoxic activity was highest for MDR-TB patients. CONCLUSIONS: CD8+ T cells from MDR-TB patients showed an exaggerated cytotoxic activity after antigenic stimulation. Further studies are required to elucidate the role of this response in the immunopathogenesis of MDR-TB.

Riesgo cardiovascular en adultos con síndrome de apnea obstructiva del sueño: a 25 años de los primeros estudios de asociación / Cardiovascular risk among adults with obstructive sleep apnea syndrome

Las enfermedades cardiovasculares y los trastornos respiratorios durante el sueño representan un grave problema de salud pública en México y el mundo. En los últimos 25 años se han realizado estudios que demuestran que el síndrome de apnea obstructiva del sueño (SAOS) es un factor de riesgo independiente para hipertensión arterial sistémica, cardiopatía isquémica y enfermedad vascular cerebral. Se ha descrito también otras asociaciones con hipertensión arterial pulmonar, arritmias, muerte súbita durante el sueño e insuficiencia cardiaca. El tratamiento con presión positiva continua en la vía aérea en pacientes con SAOS ha mostrado tener un efecto positivo sobre la prevención primaria y secundaria de las principales enfermedades cardiovasculares. En este manuscrito revisamos la evidencia epidemiológica que relaciona el SAOS con incremento en el riesgo cardiovascular y proponemos algunas estrategias para hacer frente al creciente problema del SAOS en su asociación con enfermedades cardiovasculares.

Cardiovascular diseases and sleep-disordered breathing have been recognized as a public health problem in Mexico and worldwide. These two groups of disorders are closely associated and the evidence accumulated over the last 25 years indicates that obstructive sleep apnea syndrome (OSAS) is an independent risk factor in systemic arterial hypertension, coronary artery disease and stroke. Other associations have also been described, linking these disorders with pulmonary hypertension, cardiac arrhythmias, sudden death during sleep and congestive heart failure. Treatment with continuous positive airway pressure in patients with OSAS has proven to be an efficient primary and secondary cardiovascular prevention strategy. This article reviews the epidemiological evidence that links OSAS with increased cardiovascular risk, and proposes strategies designed to address this growing health problem.

[Pleural mesothelioma in a Mexican population: clinical and radiological similarities among histopathologic patterns]. / Mesotelioma pleural. Similitudes clínico-radiológicas entre estirpes.

OBJECTIVE: To describe clinical and radiological features of patients with pleural mesothelioma, according to main histological types. METHODS: Clinical records of inpatients admitted with diagnosis of pleural mesothelioma to the Instituto Nacional de Enfermedades Respiratorias in the last 11 years, were reviewed. RESULTS: We analyzed 85 cases confirmed by immunohistochemistry. The most frequent histological type was epithelial (84.7 %), followed by sarcomatous (12.9 %) and mixed (2.4 %) types. Comparison between epithelial and sarcomatous types showed no differences in age (53.7 +/- 13.1 vs. 55.9 +/- 11.0 years, respectively), male : female ratio (2.3 : 1 vs. 1.8 : 1), history of asbestos exposure (34.7 vs. 27.2 %), tobacco habit (54.2 vs 45.4 %), occupation, evolution time (4.8 +/- 3.3 vs. 4.4 +/- 3.7 months), pain, dyspnea and cough, right-side predominance (55.6 vs. 81.8 %), radiological image with pleural effusion (59.7 vs. 36.4 %) or pleural thickening (38.9 vs. 63.6 %), and diagnostic efficiency of closed pleural biopsy (58.3 vs. 27.2 %). CONCLUSIONS: Our results suggest that clinical and radiological features of epithelial and sarcomatous histological types are very similar. Additionally, we found a high frequency of epithelial mesothelioma, which contrasts with findings from other countries, suggesting that the type of asbestos or other factors involved in the development of pleural mesothelioma differ from those existing in other regions of the world.

Differences in cardiopulmonary exercise test results by American Thoracic Society/European Respiratory Society-Global Initiative for Chronic Obstructive Lung Disease stage categories and gender.

BACKGROUND: The American Thoracic Society (ATS)/European Respiratory Society (ERS)-Global Initiative for Chronic Obstructive Lung Disease (GOLD) has developed a new staging system based on the degree of airflow obstruction. Its validity to predict exercise capacity as an outcome has not been extensively studied. We hypothesized that exercise performance measured by cardiopulmonary exercise test (CPET) results should decline significantly with each disease stage, independent of gender. METHODS: We examined 453 consecutive incremental CPET and pulmonary function tests performed in patients who had been referred to a single respiratory physiology laboratory in a tertiary care hospital. They were divided into a control group (normal lung function) and ATS/ERS-GOLD stages 1 to 4. We measured anthropometrics, peak work (in watts), peak oxygen uptake (in liters per kilogram per minute and percent predicted), breathing reserve (in percent predicted), and arterial blood gas response. We compared these results between different stages and genders. RESULTS: The mean (+/- SD) age for the entire group was 64 +/- 11 years, the mean FEV(1) was 66 +/- 28%, and the mean body mass index (BMI) was 27.2 +/- 5.82 kg/m(2). Patients in stage 4 were significantly younger (p < 0.001) and had a lower BMI (p < 0.02) compared to those in stages 1 to 3. There was a significant reduction in exercise capacity for patients at every stage except for those in stage 1, who had values similar to those of the control group. Women had better lung function and exercise capacity than men, but the difference disappeared when adjusted by COPD stages. CONCLUSIONS: The ATS/ERS-GOLD staging system can be used to indicate differences in exercise capacity in patients with COPD stages 2 to 4 and to normalize apparent gender disparities. The value of differentiating stage 1 patients requires further studies with different outcomes.