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.

Oral hygiene and dental status as factors related to asthma in high school and college students.

OBJECTIVE: Considering that oral microbiota might modulate immune responses, we explored if customary oral care procedures might influence immune-driven diseases such as asthma. METHODS: This was a retrospective, cross-sectional analysis of responses to a self-completion medical questionnaire applied to subjects entering into college and high school programs during 2006-2011. RESULTS: Responses from 329 780 students aged 14-24 years (97.6% of the original population) were analyzed. The prevalence of lifetime asthma was 4.01%. Subjects with asthma were slightly older, taller and heavier than subjects without asthma, and these differences were equally present in males and females. Subjects currently having two or more decayed teeth had asthma less frequently than those with one or none decayed tooth, with an odds ratio (OR) = 0.86 and 95% confidence interval (95% CI) 0.83-0.89. In contrast, asthma was reported more frequently among students having two or more missing or filled teeth [OR = 1.1 (95% CI 1.04-1.17) and OR = 1.05 (95% CI 1.01-1.09), respectively]. From 2008 onwards, subjects also responded questions about oral hygiene incorporated into the core questionnaire. In these subjects, the use of toothpaste as well as the frequency and duration of toothbrushing were unrelated to asthma; regular use of mouthwash was associated with asthma in women [OR = 1.16 (95% CI 1.07-1.25)], but not in men [OR = 1.04 (95% CI 0.96-1.13)]. Results of multiple logistic regressions were in line with these findings. CONCLUSIONS: Our results suggested that oral hygiene and dental status could be novel factors influencing asthma development, and thus further studies to confirm and clarify this association are warranted.

[Epidemiological trends 1992-2007 in a neonatal intensive care unit]. / Cambios epidemiológicos de 1992 a 2007 en una unidad de cuidados intensivos neonatales.

INTRODUCTION: progressive advances in neonatal care are expected to change the epidemiological profile of patients and conditions seen in neonatal intensive care units (NICU). Thus, the objective of this study was to identify such changes in a NICU in Mexico City. METHODS: retrospectively, we analyzed age, gender, weight at admission, hospital stay,diagnoses at discharge and cause of death in 5,192 patients admitted from 1992-2007. RESULTS: in the study period,patients were admitted at a progressively older age (median of 3 days old in 1992 to 9 in 2007; rS = 0.87) and lower weight (2,800-2,343 g; rS = ­0.56), while length of hospital stay was stable (approximately, 9 days). Over 90% patients had cardiological, digestive and/or pulmonary diseases, and most patients (71.4%) had conditions for which a surgical approach is the usual treatment. Cardiological and neurologic problems increased (rS = 0.86 and 0.85, respectively),while pulmonary diseases decreased (rS = ­0.79). Mortality and autopsy rate diminished from 26 to 15% (rS = ­0.80),and from 32.5 to 10.7% (rS = ­0.53), respectively. Conditions more frequently associated with death were urologic/nephrologic and infectious diseases. CONCLUSION: epidemiological patterns in our NICU are clearly changing, and thus searching for similar time trends in other NICU is warranted.

Reference values for airway resistance in newborns, infants and preschoolers from a Latin American population.

BACKGROUND AND OBJECTIVE: Several studies have determined reference values for airway resistance measured by the interrupter technique (Rint) in paediatric populations, but only one has been done on Latin American children, and no studies have been performed on Mexican children. Moreover, these previous studies mostly included children aged 3 years and older; therefore, information regarding Rint reference values for newborns and infants is scarce. METHODS: Rint measurements were performed on preschool children attending eight kindergartens (Group 1) and also on sedated newborns, infants and preschool children admitted to a tertiary-level paediatric hospital due to non-cardiopulmonary disorders (Group 2). RESULTS: In both groups, Rint values were inversely associated with age, weight and height, but the strongest association was with height. The linear regression equation for Group 1 (n = 209, height 86-129 cm) was Rint = 2.153 - 0.012 × height (cm) (standard deviation of residuals 0.181 kPa/L/s). The linear regression equation for Group 2 (n = 55, height 52-113 cm) was Rint = 4.575 - 0.035 × height (cm) (standard deviation of residuals 0.567 kPa/L/s). Girls tended to have slightly higher Rint values than boys, a difference that diminished with increasing height. CONCLUSIONS: In this study, Rint reference values applicable to Mexican children were determined, and these values are probably also applicable to other paediatric populations with similar Spanish-Amerindian ancestries. There was an inverse relationship between Rint and height, with relatively large between-subject variability.

Endoscopy for the initial suspicion of vascular rings in tracheoesophageal compressions: correlation with surgical findings.

UNLABELLED: Vascular rings (VR) may produce extrinsic compression of trachea and/or esophagus. Diagnosis relies on nonspecific clinical data from resulting compression and image studies, mainly angiography, computed tomography, and cardiovascular MRI. Because of their low incidence, diagnosis is often missed. The role of bronchoscopy and esophagoscopy is controversial, but these procedures might establish for the first time the diagnostic suspicion of VR. This communication was aimed to determine to what extent endoscopic manifestations lead the clinician to suspect the presence of a VR and, moreover, to define their correlation with surgical findings. METHODS: Children with endoscopic diagnosis of VR submitted to surgery were retrospectively analyzed. RESULTS: Twenty patients fulfilled inclusion criteria. They were submitted to 19 bronchoscopies and 16 esophagoscopies, and in 60% cases they raised the first suspicion of VR. Diagnostic agreement of the type of VR between endoscopy and surgery was 85%. Bronchoscopy diagnosed 12 VR, and in 10 cases predicted the specific type of VR. Additional relevant findings were detected in nine patients (47.4%). Esophagoscopy diagnosed VR in 14 patients, predicted the specific type in 78.6% and detected all aberrant right subclavian artery cases. CONCLUSIONS: Initial suspicion of VR was raised by bronchoscopic and/or esophagoscopic findings in 60% cases. Endoscopy proved to be a valuable tool to anticipate the type of malformation and to disclose associated abnormalities.

Cutoff value of lipid-laden alveolar macrophages for diagnosing aspiration in infants and children.

Chronic passage of gastric and/or alimentary material into the airways is a frequent and difficult-to-diagnose condition. Because alveolar macrophages phagocytose aspirated material, it has been suggested that their identification is a useful diagnostic method. To know the usefulness of the lipid-laden alveolar macrophages (LLAM) index as a diagnostic tool for aspiration, children from 1 month to 16 years of age were included in three groups: G-I, children with pulmonary pathology and suspicion of aspiration by clinic or image evaluation; G-II, with pulmonary pathology without suspicion of aspiration; and G-III, without respiratory symptoms nor suspicion of aspiration. Bronchoalveolar lavage was obtained through bronchoscopy in G-I and G-II, and through endotracheal tube in G-III, and the LLAM index (0-400) was determined. A total of 112 patients (41, 30, and 41 in G-I to III, respectively) were studied. LLAM index (mean +/- SEM) was highest in G-I (233.2 +/- 5.5), as compared with G-II (187.8 +/- 11.6, P < 0.05), and G-III (108.5 +/- 13.5, P < 0.001). However, notable overlap of LLAM values was observed between G-I and G-II, and between G-II and G-III. When patients from G-I and G-III were jointly analyzed, the area under the ROC curve for diagnosing aspiration was 0.92, with a best cutoff value of >165 (98.6% sensitivity, 78.0% specificity, 87.8% overall accuracy). LLAM index, with a cutoff value of >165 is a useful diagnostic test for aspiration when there is suspicion of this condition. However, due to its low specificity, it does not discriminate other causes of chronic lung disease.

Efecto de la rhDNasa sobre la obstrucción bronquial irreversible en adultos con asma grave / Effect of rhDNase on irreversible bronchial obstruction in severe adult asthma

Introducción: En algunos pacientes asmáticos la obstrucción de las vías aéreas no puede ser revertida por tratamiento broncodilatador y/o corticosteroideo. Esta obstrucción irreversible se ha atribuido a la remodelación de las vías aéreas, pero otros mecanismos, como el taponamiento mucoso, no se han explorado. Objetivo: Evaluar si la rhDNasa, enzima ampliamente usada para fluidificar el moco respiratorio en la fibrosis quística, mejora las variables espirométricas y la calidad de vida de pacientes con asma grave. Pacientes y métodos: Diez pacientes adultos (6 mujeres) con asma grave, dependientes de corticosteroides, recibieron nebulizaciones diarias de 2.5 mg de rhDNasa durante 14-28 días. Se realizaron espirometrías por lo menos cada semana, evaluando la capacidad vital forzada (FVC), el volumen espiratorio forzado al primer segundo (FEV1, la relación FEV1/ FVC y el flujo espiratorio máximo (PEF). Los cambios espirométricos se evaluaron mediante análisis de regresión. Se aplicó un cuestionario de calidad de vida antes y al final del tratamiento. Resultados: Las variables espirométricas no cambiaron en la mayoría de los pacientes. Sin embargo, al menos un paciente tuvo mejoría de la función pulmonar, de acuerdo con las pendientes ascendentes estadísticamente significativas en la FVC, el FEV1 y la relación FEV1/FVC. Aunque otros sujetos también tuvieron cambios ascendentes (2 pacientes) o descendentes (2 pacientes) de las pendientes, éstos sólo ocurrieron en una de las variables espirométricas. Como grupo, los pacientes mostraron tendencia a la mejoría en la calidad de vida. Conclusiones: Aunque la rhDNasa no modifica la obstrucción bronquial irreversible en la gran mayoría de los pacientes con asma grave, una pequeña proporción de ellos podría obtener algún efecto benéfico.

Background: In some asthma patients airway obstruction can not be reverted by bronchodilator and/ or corticosteroid treatment. This irreversible obstruction has been attributed to the remodeling process of airways, but other mechanisms such as mucus plugging have not been explored. Objective: To evaluate if rhDNase, an enzyme extensively used to fluidize the mucus in cystic fibrosis, improves spirometric variables and quality of life of asthmatic patients. Patients and methods: Ten adult patients (6 females) with severe corticosteroid-dependent asthma received daily nebulizations of 2.5 mg rhDNase during 14-28 days. Spirometries were performed at least at weekly intervals to evaluate the forced vital capacity (FVC), forced expiratory flow at the first second (FEV1, the FEV1/FVC ratio and peak expiratory flow (PEF). Changes in spirometric variables were assessed by regression analysis. An asthma quality of life questionnaire was applied before and at the end of treatment. Results: Spirometric variables did not change in most patients. However, pulmonary function improved in one patient, according to the statistically significant ascending slopes in FVC, FEV1 and FEV1/FVC. Although other subjects also had ascending (2 patients) or descending (2 patients) slopes, these changes only occurred in one spirometric variable. As a group, there was a trend for improvement in quality of life. Conclusions: Although rhDNase does not modify the irreversible bronchial obstruction in most patients with severe asthma, a small proportion of them might obtain some beneficial effect.

Underestimation of the peak flow variability in asthmatic children: evaluation of a new formula.

Asthma guidelines suggest evaluation of peak expiratory flow (PEF) variability, but timing for the two PEF measurements is not mentioned. Usual formula calculates amplitude as percentage of mean day-night PEF values. Since PEF circadian changes follow a sinusoidal function, we reasoned that variability might be calculated by measuring PEF at 4 pm (PEF(1)) and either at 10 am or 10 pm (PEF(2)) with the formula %variability = 200 . |PEF(1)-PEF(2)|/PEF(2). Children with stable, mild intermittent asthma were recruited from an Asthma Clinic and asked to perform PEF measurements at even hours during a week, until 12 measurements covering a 24-h period were accomplished. From these measurements we calculated PEF variability through several methods. Accuracy of such methods to predict actual PEF variability was assessed through the concordance correlation coefficient (r(c)). Thirty five asthmatic children were recruited. Actual PEF variability, calculated with the usual formula using the highest and lowest PEF obtained at any time of the 24 h cycle had a median of 37.3% (range, 0-88.5%). Variability calculated through other methods was: usual formula with highest and lowest PEF obtained from the sinusoidal curve, 21.4% (r(c) = 0.79); usual formula with PEF measured at 4 pm and 4 am, 17.8% (r(c) = 0.67); proposed formula using PEF measured at 4 pm and either 10 pm, 15.9% (r(c) = 0.68), or 10 am, 17.4% (r(c) = 0.69). Some examples with PEF measured in the morning (8 am or 10 am) and at night (8 pm or 10 pm) yielded median PEF variability from 4.0% (r(c) = 0.18) to 8.7% (r(c) = 0.38). Current methods for calculating PEF variability seemed not to be accurate enough as to be confident, suggesting that an in-deep reevaluation of the usefulness of PEF variability or, conversely, of the methods to assess it, should be done.

Evaluation of antihypoxemic maneuvers before tracheal aspiration in mechanically ventilated newborns.

Periodical tracheal aspiration in mechanically ventilated patients is necessary to remove mucus from the airways. In children and adults, this procedure causes transient hypoxemia, which may be prevented by hyperoxia and/or hyperventilation. These findings, however, have not been sufficiently assessed in newborn infants. Thus we investigated the usefulness of hyperoxia and/or hyperventilation as antihypoxemic maneuvers before tracheal aspiration in newborn infants. Our design was a prospective, randomized, multiple crossover study. The setting was the NICU of a third-level pediatric hospital in Mexico City. Patients included 15 newborn infants under mechanical ventilation. Within a 12-hr period, every patient received, in random order, three antihypoxemic maneuvers during 1 min just before tracheal aspiration: hyperoxia (10% increase of baseline FiO2), hyperventilation (50% increase of ventilator cycling rate), or both. Additionally, a control (sham) maneuver was also applied. Pulse oximeter saturation (SpO2) was recorded before and after each antihypoxemic maneuver, and at 0, 15, 30, 60, and 300 sec after tracheal aspiration. Basal values of SpO2 (81.5 +/- 1.5%) increased with all three antihypoxemic maneuvers (SpO2 over 90%, P <0.05 to P <0.01). Immediately after tracheal aspiration a drop in the SpO2 could be detected in all infants. However, patients receiving hyperoxia showed higher SpO2 values (87.1 +/- 1.8%) than those observed with the sham maneuver (76.9 +/- 2.3%, P <0.01). From this point on, all newborn infants in all conditions (even those with sham maneuver) had spontaneous increments of SpO2 that at 300 sec were again higher than their respective basal values (P <0.05 to P <0.0005). At this time, SpO2 values from following the hyperoxia maneuver were still higher than those following the sham maneuver (P <0.05). Our results show that, similar to what occurs at other ages, tracheal aspiration in mechanically ventilated newborn infants causes transient hypoxemia, which can be partially prevented by previous application of antihypoxemic maneuvers, especially hyperoxia.

Trends of asthma in Mexico: an 11-year analysis in a nationwide institution.

STUDY OBJECTIVES: Asthma prevalence is increasing in many countries. Some recent articles, however, claim that this tendency is ending. Our aim was to investigate asthma trends in Mexico. DESIGN: Annual data on health services provided to asthmatic patients were retrospectively analyzed from 1991 to 2001. SETTING: The Instituto Mexicano del Seguro Social, the largest nationwide medical institution in Mexico (approximately 24 to 32 million insured subjects). PARTICIPANTS: Health services provided to subjects of any age. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Asthma-associated health services, either expressed as absolute number or as rate per insured subjects, progressively increased until 1997 in family physician office visits (FPOVs) [newly diagnosed cases only], emergency department visits (ERVs), and hospital discharges (HDs). From that year onward, the number and rates of asthma-associated health services decreased. The same trends were observed for age groups 0 to 4 years, 5 to 14 years, 15 to 44 years, and 45 to 64 years. Using a different approach, asthma was diagnosed each year in approximately 0.4% of all FPOVs, but a decrease in this percentage was observed from 1997 onward. Likewise, asthma caused increasing percentages of all ERVs and HDs until 1997, followed by a sharp decline thereafter. CONCLUSIONS: A decline in absolute and relative numbers of asthma-associated health services occurred over recent years in all medical settings, suggesting that the epidemic of new asthma cases is ending and/or that better control of the disease has been achieved.

Sweat conductivity and chloride titration for cystic fibrosis diagnosis in 3834 subjects.

Sweat test is the standard for cystic fibrosis (CF) diagnosis. Conductivity is an alternative method not yet approved, in spite of its good correlation with chloride concentration. The aim was to assess the capacity of sweat conductivity to discriminate between CF and non-CF subjects. Automated measurements of conductivity and chloride concentration were carried out on the same sweat samples from subjects with clinical suspicion of CF. Sweat samples from 3,834 subjects, median age 1.8 years (range 1 month-54 years) were analysed, and those with chloride titration >60 mmol/l were considered as CF patients (n=294). Conductivity median values in CF and non-CF subjects were 111 mmol/l (82-148) and 36 mmol/l (12-89), respectively. The Spearman correlation between chloride titration and conductivity was r=0.60 (P<0.001). The receiver operating characteristics (ROC) curve showed very high agreement between two methods. The best conductivity cut-off value to diagnose CF was > or =90 mmol/l (sensitivity 99.7%, specificity 100%, positive and negative predictive values of 100% and 99.97%, respectively, and kappa=0.998). Likewise, the best conductivity cut-off value to exclude CF was <75 mmol/l. The sweat conductivity method showed good correlation with chloride titration, and accurately discriminated between subjects with and without CF. In accordance with this, CF diagnosis might be confirmed for conductivity values > or =90 mmol/l and excluded for <75 mmol/l. Values between 75 and 89 mmol/l should correspond to an equivocal range. However, more studies are needed to confirm the role of conductivity in definitive CF diagnosis.