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.

Mesenchymal stem cells attenuate the proinflammatory cytokine pattern in a guinea pig model of chronic cigarette smoke exposure.

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.

Cystic and pseudocystic pulmonary malformations in children: Clinico-pathological correlation.

Pulmonary malformations are rare disorders, with cystic and pseudocystic pulmonary malformations (CPPM) the most frequent, and constitute the first cause of lobectomy in children <1 year of age. Morphological overlap of congenital cystic pulmonary lesions might correspond to a spectrum of lesions in which bronchial atresia is a common etiopathogenetic mechanism. We aimed to report the frequency of CPPM resected in a tertiary-level hospital and to evaluate the degree of agreement between presurgical and anatomopathological diagnoses. We studied 44 surgical pieces with a diagnosis of CPPM received at the Pathology Service from 2009 to 2014, resected from 39 patients, 51.3 % males, with a median age of 16.8 months. Up to 69.2% of the patients had adenomatoid malformation of pulmonary airway (AMPA), with type 2 the most frequent (55.5%). Pulmonary sequestration was present in 15.4% of patients; in two cases the diagnosis was an incidental finding during surgery for the repair of a diaphragmatic hernia. Congenital lobar hyperinflation (CLH) occurred in 7.6% cases. Bronchogenic cyst (BC) was present in 7.6% cases. Presurgical and anatomopathological diagnoses in all patients coincided in 71.8% of cases. Kappa coefficient was 0.56 for global concordance in patients with AMPA, and 0.72, 0.64, 0.37 and 0.33 for CLH, BC, and types 1 and 2 AMPA, respectively. This relatively low interobserver agreement could reflect the low reproducibility of diagnoses used in the current nomenclature. Thus, the new nomenclature must be promoted in order to allow for better reproducibility and greater clinico-pathological concordance. The anatomopathological analysis must include the intentional search for bronchial atresia.

Allergic sensitization increases the amount of extracellular ATP hydrolyzed by guinea pig leukocytes.

Increased levels of ATP have been found in the bronchoalveolar lavage of patients with asthma, and subjects with this disease, but not healthy subjects, develop bronchospasm after nebulization with ATP. Because the main mechanism for controlling the noxious effects of extracellular ATP is its enzymatic hydrolysis, we hypothesized that allergic sensitization is accompanied by a decreased functioning of such hydrolysis. In the present study, peripheral blood leukocytes from sensitized and non-sensitized guinea pigs were used for determining the extracellular metabolism (as assessed by inorganic phosphate production) of ATP, ADP, AMP, or adenosine, and for detecting possible changes in the expression (qPCR and Western blot) of major ectonucleotidases (NTPDase1, NTPDase3, and NPP1) and purinoceptors (P2X1, P2X7, P2Y4, and P2Y6). Contrary to our hypothesis, we found that leukocytes from allergic animals produced higher amounts of inorganic phosphate after stimulation with ATP and ADP, as compared with leukocytes from non-sensitized animals. Although at first glance, this result suggested that sensitization caused higher efficiency of ectonucleotidases, their mRNA and protein expressions were unaffected. On the other hand, after sensitization, we found a significant increase in the protein expression of P2X7 and P2Y4, two purinoceptors known to be responsible for ATP release after activation. We concluded that allergic sensitization increased the amount of ATP hydrolyzed by ectonucleotidases, the latter probably not due to the enhanced efficiency of its enzymatic breakdown, but rather due to an increased release of endogenous ATP or other nucleotides, partly mediated by enhanced expression or P2X7 and P2Y4 receptors.

Causal inference with multiple concurrent medications: A comparison of methods and an application in multidrug-resistant tuberculosis.

This paper investigates different approaches for causal estimation under multiple concurrent medications. Our parameter of interest is the marginal mean counterfactual outcome under different combinations of medications. We explore parametric and non-parametric methods to estimate the generalized propensity score. We then apply three causal estimation approaches (inverse probability of treatment weighting, propensity score adjustment, and targeted maximum likelihood estimation) to estimate the causal parameter of interest. Focusing on the estimation of the expected outcome under the most prevalent regimens, we compare the results obtained using these methods in a simulation study with four potentially concurrent medications. We perform a second simulation study in which some combinations of medications may occur rarely or not occur at all in the dataset. Finally, we apply the methods explored to contrast the probability of patient treatment success for the most prevalent regimens of antimicrobial agents for patients with multidrug-resistant pulmonary tuberculosis.

Effect of oral glycine on the clinical, spirometric and inflammatory status in subjects with cystic fibrosis: a pilot randomized trial.

BACKGROUND: Patients with cystic fibrosis (CF) have airway inflammation that contributes to symptoms and to pulmonary function derangement. Current drugs used to diminish airway inflammation improve the clinical and spirometric status of patients with CF, but their use is limited due to their undesired side effects, for example, glucose intolerance, growth retardation, and cataracts with corticosteroids, gastrointestinal toxicity with ibuprofen, and macrolide resistance with azythromycin. Glycine is known to decrease activation of inflammatory cells, including alveolar macrophages and neutrophils, and is relatively inexpensive, palatable, and virtually devoid of untoward effects. These features make glycine a good candidate for antiinflammatory treatment of CF. Thus, we aimed to explore whether glycine can exert a beneficial effect in a population of patients with CF. METHODS: This was a randomized, double blinded, cross-over pilot clinical trial. Subjects with CF received, in random order, oral glycine (0.5 g/kg/day, dissolved in any liquid) and placebo (glass sugar), each during 8 weeks with an intermediate 2-week wash-out period. RESULTS: Thirteen subjects aged 6-23 years, 8 females, completed the two arms of the study. As compared with placebo, after glycine intake patients had better symptom questionnaire scores (p = 0.02), mainly regarding sputum features and dyspnea. While spirometric variables tended to decline during placebo intake, they remained stable or even increased during glycine treatment (p = 0.04 to p = 0.003). In this context, FEV1 declined 8.6% after placebo and increased 9.7% at the end of the glycine period. Pulse oximetry improved after glycine intake (p = 0.04 vs. placebo). TNF-α in serum and IL-6 and G-CSF in sputum tended to decline at the end of the glycine period (p = 0.061, p = 0.068 and p = 0.04, respectively, vs placebo). Glycine was remarkably well tolerated. CONCLUSIONS: The clinical, spirometric and inflammatory status of subjects with CF improved after just 8 weeks of glycine intake, suggesting that this amino acid might constitute a novel therapeutic tool for these patients. Thus, further studies are warranted. TRIAL REGISTRATION: www.clinicaltrials.gov , registration number: NCT01417481 , date of registration: March 12, 2012.

Characteristic plethysmographic findings in a guinea pig model of COPD.

AIM OF THE STUDY: Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. MATERIALS AND METHODS: Female guinea pigs were exposed to the smoke of 20 cigarettes/day, 5 days/week, during 10 weeks (COPD group, n = 8), and were compared with unexposed female guinea pigs of the same age (control group, n = 8). WBP was performed in both groups, followed by lung histology. RESULTS: At the end of the exposure period, guinea pigs in the COPD group had higher respiratory frequency, while duty cycle (Ti/Ttot) was unaffected. There was a trend toward minute ventilation (MV) and expiratory flow at the mid-tidal volume (EF50) to be higher in the COPD group. Enhanced pause (Penh) was lower, while time of braking (TB) and time to PEF relative to Te (Rpef) were higher in the COPD group. All guinea pigs exposed to tobacco smoke developed emphysematous lesions in their lungs and gained less body weight than controls. CONCLUSIONS: In this COPD model, exposure to cigarette smoke produced changes in WBP characterized by a shallow breathing pattern with decreased Penh and a trend toward increasing EF50 (probably due to decreased elastic recoil), increased TB (suggesting dynamic laryngeal narrowing), and a trend of increasing MV (probably due to a higher metabolic rate). Many of these functional changes resemble those observed in patients with COPD and corroborate the suitability of this guinea pig model for the study of COPD.

Prevalence and Characteristics of Exercise-Induced Bronchoconstriction in High School and College Athletes at 2,240 m Altitude.

BACKGROUND: Athletes practicing strenuous physical activities may develop exercise-induced bronchoconstriction (EIB). We aimed to determine the prevalence and features of this condition in Mexico City (altitude, 2,240 m). METHODS: In the present study, 208 high school and college athletes performed a standardized EIB test on a treadmill. RESULTS: Responses to exercise had large between-subject variability in all physiological parameters (forced expiratory volume in one second [FEV1], heart rate, blood oxygen saturation level [SpO2], blood pressure), with nearly similar proportions of subjects in whom FEV1 increased or decreased. According to the recommended cut-off value of 10% FEV1 decrease, only 15 (7.2%) athletes had a positive EIB test. Weight lifters were more prone to develop EIB (three out of seven athletes; p = 0.01). Subjects with a positive EIB test already had a lower baseline forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio (96.4 vs. 103.2% of predicted, respectively; p = 0.047), and developed more respiratory symptoms after exercise than subjects with a negative test. There were no differences with respect to age, gender, body mass index, history of asthma or atopic diseases, smoking habit, and exposure to potential indoor allergens. CONCLUSIONS: The relatively low prevalence of EIB in athletes from Mexico City raises the possibility that high altitude constitutes a protective factor for EIB. In contrast, weight lifters were especially prone to develop EIB, which suggests that repetitive Valsalva maneuvers could be a novel risk factor for EIB. There was a large between-subject variability of all physiological responses to exercise.

Unsuspected Lung Pathology in Autopsies of Children with Cancer.

BACKGROUND: Although pulmonary involvement is common in patients with cancer, its frequency and nature is seldom reported in the medical literature. OBJECTIVE: To determine the frequency and type of lung pathological conditions revealed by autopsy in children with cancer. METHODS: All reports from autopsies performed in children with cancer from 1989 to 2012 in a pediatric hospital were reviewed. RESULTS: In the analyzed period, 118 autopsies (10.2% of all autopsies) corresponded to children who died with cancer; 76 had complete information and were included in the analysis. Children were seen in the Hematology (41 cases) or the Oncology (35 cases) services. Their median age at decease was 7 years (range, 15 days to 16.1 years) and 46.1% were females. Main diagnoses were acute lymphoblastic (31 patients) or myeloblastic (10 patients) leukemias and tumors of the central nervous system (12 patients). A pathological respiratory condition was diagnosed antemortem in 31 (40.8%) patients, and at autopsy in 62 (81.6%) cases. Omitted diagnoses occurred in 58 (76.3%) children, being pneumonia (24 cases) and pulmonary hemorrhage (23 cases) the most frequent omissions. Nine patients had clinically unsuspected tumor infiltration or metastases. CONCLUSIONS: In these children with cancer, more than 80% of autopsies revealed some lung pathology, mainly of infectious or hemorrhagic nature. Thus, pulmonary involvement should be investigated in all children with cancer in a timely and intentional manner.

Increased Expression of CC16 in Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology. The pathogenic mechanisms are unclear, but evidence indicates that aberrantly activated alveolar epithelial cells secrete a variety of mediators which induce the migration, proliferation and activation of fibroblasts and finally the excessive accumulation of extracellular matrix with the consequent destruction of the lung parenchyma. CC16 (approved symbol SCGB1A1), a putative anti-inflammatory protein produced by "club" cells in the distal airways, has not been evaluated in IPF lungs. In this study, we determined the serum and bronchoalveolar lavage (BAL) levels as well as the lung cell localization of this protein. Also, we explored the usefulness of serum levels of CC16 for the differential diagnosis of IPF (n = 85), compared with non-IPF interstitial lung diseases [chronic hypersensitivity pneumonitis (cHP; n = 85) and connective tissue diseases (CTD-ILD; n = 85)]. CC16 was significantly increased in serum and BAL fluids of IPF patients and was found not only in club cells but also in alveolar epithelial cells. When compared with non-IPF patients and controls, serum levels were significantly increased (p<0.0001). Sensitivity and specificity for CC16 (cut-off 41ng/mL) were 24% and 90%, positive predictive value 56% and negative predictive value 69%. These findings demonstrate that CC16 is upregulated in IPF patients suggesting that may participate in its pathogenesis. Although higher than the serum levels of non-IPF patients it shows modest sensitivity to be useful as a potential biomarker for the differential diagnosis.

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.

ATP releases ATP or other nucleotides from human peripheral blood leukocytes through purinergic P2 receptors.

AIMS: Almost every eukaryotic cell releases ATP under certain conditions. The idea that ATP induces the release of ATP has been scantly investigated. METHODS: We explored this possibility by assessing the rate of exogenous ATP breakdown (measured by phosphates production) by human peripheral blood leukocytes. The role of P2Y and P2X receptors was evaluated pharmacologically, by patch clamp, or by flow cytometry. KEY FINDINGS: In mononuclear and/or polymorphonuclear cells, ATP increased phosphates formation in a time- and concentration-dependent manner. Uncoupling of P2Y receptors with N-ethylmaleimide and antagonism of P2Y and P2X receptors through suramin reduced phosphate formation after 500µM ATP, suggesting that part of the phosphate production was due to activation of P2 receptors, with subsequent release of ATP or other nucleotides. Similar results were obtained with UTP and ATPγS. Gadolinium (connexins inhibitor) also significantly reduced the ATP-induced phosphate production. Blockade of P2X receptors with SKF 96365 or NF023 did not modify the phosphate production. In monocytes, 500µM ATP induced inward currents suggestive of P2X1 activation, but higher concentrations (1-5mM) induced inward currents suggestive of P2X7 activation. We discarded a role of adenosine in the ATP-evoked nucleotides release. Flow cytometry identified that almost all mononuclear and polymorphonuclear cells expressed P2Y1,2,4,6,11 receptors. SIGNIFICANCE: 500µM ATP induced the release of ATP or other nucleotides through activation of P2Y2,4,6,11 receptors in human leukocytes, and probably via P2X receptors at higher concentrations. This ATP-induced nucleotides release constitutes a potential mechanism leading to amplification of ATP signaling.

Clinical and epidemiological features of extrapulmonary tuberculosis in a high incidence region / Características clínicas y epidemiológicas de la tuberculosis extrapulmonar en una región de alta incidencia

Objective. To describe the clinical features of extrapulmonary tuberculosis (EXPTB) and to evaluate epidemiological data to search for potential explanations for its high frequency in the state of Aguascalientes, Mexico. Materials and methods. Clinical records of all patients with tuberculosis seen in Aguascalientes in 2008 were reviewed, and official databases were analyzed. Results. EXPTB comprised 60.5% of the 86 cases evaluated, being lymph nodes the main site affected. Patients with EXPTB were younger and more obese than subjects with pulmonary tuberculosis (PTB). One third of cases in either group had diabetes, a frequency much higher than expected. Epidemiological analysis showed that PTB incidence, but not EXPTB incidence, decreases as geographical altitude increases, and had a descendent trend from 1997 to 2011. Conclusions. The lower frequency of PTB (due to its inverse relationship with altitude and its descendent trend in last years) might explain the high frequency of EXPTB. Obesity appeared to protect against developing pulmonary involvement, and diabetes was more frequent than expected among PTB and EXPTB cases.

Objetivo. Describir las características clínicas de la tuberculosis extrapulmonar (TBEXP) y evaluar datos epidemiológicos para buscar posibles explicaciones de su alta frecuencia en Aguascalientes, México. Material y métodos. Se revisaron expedientes de todos los pacientes con tuberculosis atendidos en Aguascalientes en 2008 y se analizaron bases de datos oficiales. Resultados. La TBEXP constituyó 60.5% de los 86 casos evaluados, con afectación más común en ganglios linfáticos. Los pacientes con TBEXP fueron más jóvenes y más obesos que aquéllos con tuberculosis pulmonar (TBP). Un tercio de cada grupo tenía diabetes, una frecuencia muy superior a la esperada. El análisis epidemiológico mostró que la incidencia de TBP, pero no de TBEXP, es menor conforme aumenta la altitud geográfica y además está disminuyendo (l997-2011). Conclusiones. La menor incidencia de TBP (por su relación inversa con la altitud y por su tendencia a disminuir en los últimos años) podría explicar la alta frecuencia de TBEXP. La obesidad parece proteger contra la afectación pulmonar, y la diabetes fue más frecuente de lo esperado tanto en TBP como en TBEXP.

Type II congenital cystic pulmonary malformation in an esophageal lung.

A seven-month-old girl, born prematurely (birth weight 1000 g) from a twin pregnancy, was admitted to hospital due to recurrent pneumonia and atelectasis. She experienced cough and respiratory distress during feeding. The right hemithorax was smaller than the left, with diminished breath sounds and dullness. Chest x-rays revealed decreased lung volume and multiple radiolucent images in the right lung, as well as overdistention of the left lung. An esophagogram revealed three bronchial branches arising from the lower one-third of the esophagus, corresponding to the right lung and ending in a cul-de-sac. A diagnosis of esophageal lung was established. On bronchography, the right lung was absent and the trachea only continued into the left main bronchus. Echocardiography and angiotomography revealed agenesis of the pulmonary artery right branch. The surgical finding was an esophageal right lung, which was removed; the histopathological diagnosis was type II congenital pulmonary airway malformation in an esophageal lung.

Histamine, carbachol, and serotonin induce hyperresponsiveness to ATP in guinea pig tracheas: involvement of COX-2 pathway.

Extracellular ATP promotes an indirect contraction of airway smooth muscle via the secondary release of thromboxane A2 (TXA2) from airway epithelium. Our aim was to evaluate if common contractile agonists modify this response to ATP. Tracheas from sensitized guinea pigs were used to evaluate ATP-induced contractions before and after a transient contraction produced by histamine, carbachol, or serotonin. Epithelial mRNA for COX-1 and COX-2 was measured by RT-PCR and their expression assessed by immunohistochemistry. Compared with the initial response, ATP-induced contraction was potentiated by pretreatment with histamine, carbachol, or serotonin. Either suramin (antagonist of P2X and P2Y receptors) plus RB2 (antagonist of P2Y receptors) or indomethacin (inhibitor of COX-1 and COX-2) annulled the ATP-induced contraction, suggesting that it was mediated by P2Y receptor stimulation and TXA2 production. When COX-2 was inhibited by SC-58125 or thromboxane receptors were antagonized by SQ-29548, just the potentiation was abolished, leaving the basal response intact. Airway epithelial cells showed increased COX-2 mRNA after stimulation with histamine or carbachol, but not serotonin, while COX-1 mRNA was unaffected. Immunochemistry corroborated this upregulation of COX-2. In conclusion, we showed for the first time that histamine and carbachol cause hyperresponsiveness to ATP by upregulating COX-2 in airway epithelium, which likely increases TXA2 production. Serotonin-mediated hyperresponsiveness seems to be independent of COX-2 upregulation, but nonetheless is TXA2 dependent. Because acetylcholine, histamine, and serotonin can be present during asthmatic exacerbations, their potential interactions with ATP might be relevant in its pathophysiology.

Passive smoking induces leukotriene production in children: influence of asthma.

BACKGROUND: Passive smoking is associated with poor asthma control in children, but the mechanism is unknown. Leukotrienes are involved in the asthma pathogenesis and their synthesis is increased in adult subjects who actively smoke. OBJECTIVE: To evaluate whether passive smoking, as assessed by urinary cotinine levels, increases leukotriene production in children with or without asthma. METHODS: This was a prospective, cross-sectional study in which children with stable intermittent asthma (without exacerbation) and healthy control children were studied through spirometry and urinary concentrations of cotinine and leukotriene E(4) (LTE(4)). Both groups were balanced to include children with and without passive smoking. RESULTS: Ninety children (49 with asthma and 41 controls, 54.4% females) aged 9 years (range, 5-13 years) were studied. Urinary LTE(4) concentrations were progressively higher as cotinine levels increased (r(S) = 0.23, p = .03). LTE(4) also correlated with body mass index (BMI) (r(S) = 0.30, p = .004), and multiple regression analysis revealed that BMI was even more influential than cotinine for determining LTE(4) levels. LTE(4) concentrations were unrelated with gender, age, or spirometry. In turn, cotinine inversely correlated with forced expiratory volume in one second (FEV(1)) (r(S) = -0.22, p = .04) and forced vital capacity (FVC) (r(S) = -0.25, p = .02), but when analyzed by groups, these relationships were statistically significant only in children with asthma. CONCLUSIONS: Exposure to environmental tobacco smoke, as assessed by urinary cotinine levels, was associated with an increased urinary concentration of LTE(4), although BMI exerted more influence in determining its concentration. Urinary cotinine was associated with decreased lung function, mainly in children with asthma.

Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional / Inverse association between asthma and neural tube defects: a binational ecological study

OBJETIVO: Los donadores de metilo como el ácido fólico previenen defectos del tubo neural (DTN), pero estudios recientes sugieren que también favorecen el desarrollo de asma. En este trabajo exploramos una posible asociación ecológica entre DTN y asma. MATERIAL Y MÉTODOS: Se consultaron bases de datos de México y EUA para obtener información sobre distribución geográfica (por estado) y tendencia temporal (por año) de DTN y asma. RESULTADOS: Los estados con menor frecuencia de DTN tuvieron mayor frecuencia de asma, tanto en México (rS=-0.48, p=0.005) como en EUA (rS=-0.39, p=0.005). Las tendencias temporales también mostraron correlación inversa en México (1997-2007, rS=-0.73, p=0.01) y EUA (1979-1998, rS=-0.91, p<0.001). CONCLUSIONES: En ambos países la frecuencia de asma correlacionó de forma inversa con la frecuencia de DTN, tanto en distribución geográfica como en tendencias anuales, apoyando la posibilidad de que la ingestión de donadores de metilo en la dieta o como suplementos esté influyendo sobre la frecuencia de asma.

OBJECTIVE: Dietary intake of methyl donors such as folic acid prevents neural tube defects (NTD), but recent studies showed that it might also favor the development of asthma. In this work a possible ecological association between NTD and asthma was explored. MATERIAL AND METHODS: Data bases from Mexico and the United States (US) were reviewed to obtain information about geographical distribution (by state) and temporal trends (by year) of NTD and asthma. RESULTS: Those states with the lowest frequency of NTD had the highest frequency of asthma, both in Mexico (rS=-0.48, p=0.005) and US (rS=-0.39, p=0.005). Temporal trends also showed an inverse correlation in Mexico (1997-2007, rS=-0.73, p=0.01) and US (1979-1998, rS=-0.91, p<0.001). CONCLUSIONS: In both countries the frequency of asthma inversely correlated with the frequency of NTD, both in geographical distribution and annual trends, giving support to the possibility that methyl donors intake in diet or supplements is influencing the asthma frequency.

[Inverse association between asthma and neural tube defects: a binational ecological study]. / Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional.

OBJECTIVE: Dietary intake of methyl donors such as folic acid prevents neural tube defects (NTD), but recent studies showed that it might also favor the development of asthma. In this work a possible ecological association between NTD and asthma was explored. MATERIAL AND METHODS: Data bases from Mexico and the United States (US) were reviewed to obtain information about geographical distribution (by state) and temporal trends (by year) of NTD and asthma. RESULTS: Those states with the lowest frequency of NTD had the highest frequency of asthma, both in Mexico (rS=-0.48, p=0.005) and US (rS=-0.39, p=0.005). Temporal trends also showed an inverse correlation in Mexico (1997-2007, rS=-0.73, p=0.01) and US (1979-1998, rS=-0.91, p<0.001). CONCLUSIONS: In both countries the frequency of asthma inversely correlated with the frequency of NTD, both in geographical distribution and annual trends, giving support to the possibility that methyl donors intake in diet or supplements is influencing the asthma frequency.

Diagnoses unveiled by early bronchoscopy in children with leukemia and pulmonary infiltrates.

Pulmonary complications in children with leukemia often display nonspecific clinical and radiologic manifestations that lead to a delay in diagnosis. The role of fiberoptic bronchoscopy (FOB) and the proper time for its performance are controversial. The aim of our study was to evaluate the frequency and nature of specific diagnoses revealed by FOB. Children with leukemia submitted to FOB because of suspicion of pulmonary involvement (mainly pneumonia) were retrospectively analyzed. A total of 33 FOB procedures performed in 31 patients (20 males) with an average age of 9.4 years (range, 3.5 to 15 y) were evaluated. Microorganisms isolated from 21 (63.6%) bronchoalveolar lavage samples were mainly fungi including Candida in 13 cases (39.4%) and Aspergillus in 3 cases (9.1%). Isolation rate in 10 procedures performed within the first 3 days was 90%. Tracheobronchitis was present in > 50% of patients, pulmonary hemorrhage was seen in 7 (21.0%) patients, and leukemic infiltration was demonstrated in 2 patients (6.1%), among other conditions visualized by FOB. Complications of FOB were minimal and transient. Our study suggests that FOB is a useful and safe procedure in patients with leukemia and pulmonary infiltrates. The earlier the FOB was performed, the higher the isolation rate of causative agents. In addition, this procedure allowed the identification of noninfectious airway comorbidities. Further studies in regard to this issue are warranted.

Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disorder of unknown etiology. The disease is likely the result of complex interactions between genetic and environmental factors. Evidence suggests that certain environmental factors, such as cigarette smoking and metal dust exposures, or comorbidities like gastroesophageal reflux, and type 2 diabetes mellitus (DM2) may increase risk to develop IPF. Substantial uncertainty remains, however, regarding these and other putative risk factors for IPF. In this study we performed a case-control analysis including 100 patients with IPF and 263 controls matched for age sex and place of residence. We used a structured questionnaire to identify potential risk factors for IPF, including environmental and occupational exposures as well as the relevance of family history of pulmonary fibrosis. The multivariate analysis revealed that family history of pulmonary fibrosis [OR = 6.1, CI95% 2.3-15.9; p < 0.0001] was strongly associated with increased risk of IPF. Actually, 20% of the cases reported a parent or sibling with pulmonary fibrosis. Gastroesophageal reflux [OR = 2.9, CI: 1.3-6.6; p = 0.007], former cigarette smoking [OR = 2.5, CI: 1.4-4.6, p = 0.003], and past or current occupational exposure to dusts, smokes, gases or chemicals [OR = 2.8, CI: 1.5-5.5; p = 0.002] were also associated with the disease. Despite being a significant risk factor on univariate analysis DM2 was not significant in multivariate analysis. These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease.