Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.

CD56-mediated activation of human natural killer cells is triggered by Aspergillus fumigatus galactosaminogalactan.

Invasive aspergillosis causes significant morbidity and mortality in immunocompromised patients. Natural killer (NK) cells are pivotal for antifungal defense. Thus far, CD56 is the only known pathogen recognition receptor on NK cells triggering potent antifungal activity against Aspergillus fumigatus. However, the underlying cellular mechanisms and the fungal ligand of CD56 have remained unknown. Using purified cell wall components, biochemical treatments, and ger mutants with altered cell wall composition, we herein found that CD56 interacts with the A. fumigatus cell wall carbohydrate galactosaminogalactan (GAG). This interaction induced NK-cell activation, degranulation, and secretion of immune-enhancing chemokines and cytotoxic effectors. Supernatants from GAG-stimulated NK cells elicited antifungal activity and enhanced antifungal effector responses of polymorphonuclear cells. In conclusion, we identified A. fumigatus GAG as a ligand of CD56 on human primary NK cells, stimulating potent antifungal effector responses and activating other immune cells.

Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen.

Infections and disease caused by the obligate human pathogen Bordetella pertussis (Bp) are increasing, despite widespread vaccinations. The current acellular pertussis vaccines remain ineffective against nasopharyngeal colonization, carriage, and transmission. In this work, we tested the hypothesis that Bordetella polysaccharide (Bps), a member of the poly-ß-1,6-N-acetyl-D-glucosamine (PNAG/PGA) family of polysaccharides promotes respiratory tract colonization of Bp by resisting killing by antimicrobial peptides (AMPs). Genetic deletion of the bpsA-D locus, as well as treatment with the specific glycoside hydrolase Dispersin B, increased susceptibility to AMP-mediated killing. Bps was found to be both cell surface-associated and released during laboratory growth and mouse infections. Addition of bacterial supernatants containing Bps and purified Bps increased B. pertussis resistance to AMPs. By utilizing ELISA, immunoblot and flow cytometry assays, we show that Bps functions as a dual surface shield and decoy. Co-inoculation of C57BL/6J mice with a Bps-proficient strain enhanced respiratory tract survival of the Bps-deficient strain. In combination, the presented results highlight the critical role of Bps as a central driver of B. pertussis pathogenesis. Heterologous production of Bps in a non-pathogenic E. coli K12 strain increased AMP resistance in vitro, and augmented bacterial survival and pathology in the mouse respiratory tract. These studies can serve as a foundation for other PNAG/PGA polysaccharides and for the development of an effective Bp vaccine that includes Bps.

Cytomegalovirus infection and disease in systemic lupus erythematosus patients at a high-complexity hospital in southwestern Colombia.

Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38 years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population.

Two-stage targeted maximum likelihood estimation for mixed aggregate and individual participant data analysis with an application to multidrug resistant tuberculosis.

In this study, we develop a new method for the meta-analysis of mixed aggregate data (AD) and individual participant data (IPD). The method is an adaptation of inverse probability weighted targeted maximum likelihood estimation (IPW-TMLE), which was initially proposed for two-stage sampled data. Our methods are motivated by a systematic review investigating treatment effectiveness for multidrug resistant tuberculosis (MDR-TB) where the available data include IPD from some studies but only AD from others. One complication in this application is that participants with MDR-TB are typically treated with multiple antimicrobial agents where many such medications were not observed in all studies considered in the meta-analysis. We focus here on the estimation of the expected potential outcome while intervening on a specific medication but not intervening on any others. Our method involves the implementation of a TMLE that transports the estimation from studies where the treatment is observed to the full target population. A second weighting component adjusts for the studies with missing (inaccessible) IPD. We demonstrate the properties of the proposed method and contrast it with alternative approaches in a simulation study. We finally apply this method to estimate treatment effectiveness in the MDR-TB case study.

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.

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.

Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis.

We report that in the presence of signal 1 (NF-κB), the NLRP3 inflammasome was activated by mitochondrial apoptotic signaling that licensed production of interleukin-1ß (IL-1ß). NLRP3 secondary signal activators such as ATP induced mitochondrial dysfunction and apoptosis, resulting in release of oxidized mitochondrial DNA (mtDNA) into the cytosol, where it bound to and activated the NLRP3 inflammasome. The antiapoptotic protein Bcl-2 inversely regulated mitochondrial dysfunction and NLRP3 inflammasome activation. Mitochondrial DNA directly induced NLRP3 inflammasome activation, because macrophages lacking mtDNA had severely attenuated IL-1ß production, yet still underwent apoptosis. Both binding of oxidized mtDNA to the NLRP3 inflammasome and IL-1ß secretion could be competitively inhibited by the oxidized nucleoside 8-OH-dG. Thus, our data reveal that oxidized mtDNA released during programmed cell death causes activation of the NLRP3 inflammasome. These results provide a missing link between apoptosis and inflammasome activation, via binding of cytosolic oxidized mtDNA to the NLRP3 inflammasome.

Increased risk of depression and impairment in quality of life in patients with lamellar ichthyosis.

Lamellar ichthyosis (LI) is a genetic skin disorder characterized by dark brown scales, palmoplantar hyperkeratosis, pain, and itching. LI severity could have implications in psychological aspects, causing depression and impairment in the quality of life (QoL) of patients. In this study, we used the Congenital Ichthyosis Severity Index, the Depression Beck Inventory-II (DBI-II), and the Dermatologic Life Quality Index (DLQI) to assess severity, level of depression, and impairment in QoL in a group of patients with LI. We observed that the majority of the patients presented a high severity level concerning the presence of scales (57.7%), while for erythema and alopecia, the severity was less 80% of the analyzed patients presented depression, while only 20.8% of individuals of the control group presented it (P < .001, OR = 15.2). While for QoL, only 4.3% of the patients did not exhibit any impairment. Finally, the increase in the score obtained in DBI-II was correlated with the DLQI score (rs = 0.663, P = .0014). Our results suggest that patients with LI have an increased risk of suffering depression and impairment in their QoL; thus, the management of their disease should be performed from a multidisciplinary perspective to improve the global aspects of their lives.

Electromagnetic Dosimetry for Isolated Mitochondria Exposed to Near-Infrared Continuous-Wave Illumination in Photobiomodulation Experiments.

This paper presents results on the electromagnetic field computed inside isolated mitochondria when they are exposed to near-infrared illuminations with reference to photobiomodulation experiments. The accurate calculation of the electromagnetic dose is considered to be important for a better understanding of the mechanism of interaction of light with these organelles and to improve the reliability and repeatability of the experiments. To get such results, we introduce several models. Even though they refer to a well-defined experimental setup, different models are necessary to take into account the possible different dispositions of the mitochondria, and of the differences in their dimensions and in their constitutive parameters. Different wavelengths and polarizations are considered as well. The effects of all parameters on the electromagnetic field inside mitochondria are discussed. © 2021 Bioelectromagnetics Society.

Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19.

In December 2019, a new and highly contagious infectious disease emerged in Wuhan, China. The etiologic agent was identified as a novel coronavirus, now known as Severe Acute Syndrome Coronavirus-2 (SARS-CoV-2). Recent research has revealed that virus entry takes place upon the union of the virus S surface protein with the type I transmembrane metallo-carboxypeptidase, angiotensin converting enzyme 2 (ACE-2) identified on epithelial cells of the host respiratory tract. Virus triggers the synthesis and release of pro-inflammatory cytokines, including IL-6 and TNF-α and also promotes downregulation of ACE-2, which promotes a concomitant increase in levels of angiotensin II (AT-II). Both TNF-α and AT-II have been implicated in promoting overexpression of tissue factor (TF) in platelets and macrophages. Additionally, the generation of antiphospholipid antibodies associated with COVID-19 may also promote an increase in TF. TF may be a critical mediator associated with the development of thrombotic phenomena in COVID-19, and should be a target for future study.

A world review of reported myiases caused by flower flies (Diptera: Syrphidae), including the first case of human myiasis from Palpada scutellaris (Fabricius, 1805).

Rat-tailed larvae of the syrphid species Palpada scutellaris (Fabricius, 1805) are documented causing an enteric human myiasis in Costa Rica. This is the first time that the genus Palpada is recorded as a human myiasis agent. We report a 68-year-old woman with intestinal pain and bloody diarrhea with several live Palpada larvae present in the stool. Using molecular techniques (DNA barcodes) and both electronic and optical microscopy to study the external morphology, the preimaginal stages of the fly were unambiguously identified. An identification key to all syrphid genera actually known as agents of human and animal myiases is provided for larvae, puparia, and adults. Moreover, a critical world review of more than 100 references of Syrphidae as myiasis agents is also given, with emphasis on the species with rat-tailed larvae.

Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients.

Loss to follow-up (LFU) of ≥2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU.We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan-Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU.Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3-11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36-50 years (HR 1.3, 95% CI 1.0-1.6; p=0.04) compared with age 0-25 years, being HIV positive (HR 1.8, 95% CI 1.2-2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6-1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4-0.6; p<0.01) compared with no serious adverse event.Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months.

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.

Factors related to changes in the asthma male: female ratio by age in 403 Mexican counties.

BACKGROUND: Asthma is more frequent in males during childhood and in females after adolescence, which has been attributed to changes in sexual hormones levels. OBJECTIVE: We explored changes of the asthma male: female ratio (AMFR) by age group in a large population (nationwide), and its ecological association (at county level) with some medical, geographical, or sociodemographic factors. METHODS: Registries of the largest medical institution in Mexico (∼37.5 million subjects assigned to a family physician) were analyzed and the AMFR calculated using asthma incidences. RESULTS: In boys, asthma incidence peaked at 0 to 4 years and progressively decreased, reaching a plateau in adulthood. In girls, asthma incidence showed a bimodal pattern, with maximal rates at 0 to 4 years old, and again at 50 to 54 years old. In the ecological analysis performed in more than 400 counties, the AMFR in adults (≥15 years old) inversely correlated with population density (r = -0.256) and altitude (r = -0.144), and directly correlated with acute respiratory tract infections (ARTI, r = 0.215), diabetes (r = 0.186), marginalization (r = 0.179), pneumonias (r = 0.166), and mean maximal temperature (r = 0.142), all with P < .01. In the multiple linear regression, only population density (P < .001) and ARTI (P = .006) remained statistically significant in the final model. CONCLUSION: Asthma incidence in males and females did not match the expected sexual hormones variations, and other factors such as population density and ARTI also influenced the AMFR. These findings challenge the traditional belief that sexual hormones are major determinants of the AMFR.

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.

Prevalence of Trichomonas vaginalis and Human papillomavirus in female sex workers in Central Veracruz, Mexico.

Female sex workers (FSWs) have been considered a key population for sexually transmitted infections (STIs); therefore, they are periodically screened as a requirement to obtain a work card. However, there is insufficient epidemiological data on STIs among FSWs in Mexico. The detection of Trichomonas vaginalis is limited to microscopic studies and the molecular screening of Human papillomavirus (HPV) is only done to women 35 years of age and older. The objective of this study was to determine the prevalence of T. vaginalis and HPV infections in FSWs in the city of Orizaba, Veracruz, Mexico. Samples from 105 FSWs were obtained by cervical swab and analyzed. The identification of T. vaginalis and HPV was performed by molecular methods. HPV DNA was identified in 5.71% of the samples with the presence of HPV16, HPV18, and HPV58. A percentage of 25.7% samples were positive for T. vaginalis for optical microscopy and 23.8% for PCR. The results of the study indicate the need to incorporate more sensitive methods for the timely diagnosis of STIs as well as comprehensive health promotion programs directed to the most vulnerable groups among FSWs.

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.

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.

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.