Gustavo Nino

Respiratory syncytial virus, adenoviruses, and mixed acute lower respiratory infections in children in a developing country

There is growing evidence suggesting greater severity and worse outcomes in children with mixed as compared to single respiratory virus infections. However, studies that assess the risk factors that may predispose a child to a mixture of respiratory syncytial virus (RSV) and adenoviral infections, are scarce. In a retrospective cohort study, the study investigated the epidemiology of RSV and adenovirus infections and predictors of mixed RSV‐adenoviral infections in young children hospitalized with acute lower respiratory infection in Bogota, Colombia, South America, over a 2‐year period 2009–2011. Of a total of 5,539 children admitted with a diagnosis of acute lower respiratory infection, 2,267 (40.9%) who were positive for RSV and/or adenovirus were selected. Out the total number of cases, 1,416 (62.5%) infections occurred during the 3‐month period from March to May, the first rainy season of Bogota, Colombia. After controlling for gender, month when the nasopharyngeal sample was taken, and other pre‐existing conditions, it was found that an age greater than 6 months (OR:1.74; CI 95%:1.05–2.89; Pu2009=u20090.030) and malnutrition as a comorbidity (OR:9.92; CI 95%:1.01–100.9; Pu2009=u20090.049) were independent predictors of mixed RSV‐adenoviral infections in the sample of patients. In conclusion, RSV and adenovirus are significant causes of acute lower respiratory infection in infants and young children in Bogota, Colombia, especially during the first rainy season. The identified predictors of mixed RSV‐adenoviral infections should be taken into account when planning intervention, in order to reduce the burden of acute lower respiratory infection in young children living in the country. J. Med. Virol. 87:774–781, 2015.

Cost‐utility analysis of daily versus intermittent inhaled corticosteroids in mild‐persistent asthma

Despite the many benefits that have been demonstrated by the continuous administration of inhaled corticosteroids (ICS) in persistent asthma, a new strategy for mild‐asthma is emerging, consisting of using intermittent or as‐needed ICS treatment in conjunction with short‐acting beta2 agonists in response to symptoms. However, no previous studies have reported an economic evaluation comparing these two therapeutic strategies.

The link between rhinitis and rapid-eye-movement sleep breathing disturbances in children with obstructive sleep apnea

BACKGROUNDnRhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities.nnnMETHODSnWe conducted a retrospective cross-sectional analysis of 145 children with PSG-diagnosed OSA. Outcomes included PSG parameters and obstructive apnea-hypopnea index (OAHI) during REM and non-REM. Linear multivariable models examined the joint effect of rhinitis and OSA parameters with control for potential confounders.nnnRESULTSnRhinitis was present in 43% of children with OSA (n = 63) but overall OAHI severity was unaffected by the presence of rhinitis. In contrast, OAHI during REM sleep in children with moderate-severe OSA was significantly increased in subjects with rhinitis and OSA (44.1/hr; SE = 6.4) compared with those with OSA alone (28.2/hr; SE = 3.8).nnnCONCLUSIONnRhinitis is highly prevalent in children with OSA. Although OSA is not more severe in children with rhinitis, they do have a distinct OSA phenotype characterized by more REM-related OSA. Further research is needed to delineate the link between REM-sleep and the physiology of the nose during health and disease.Background Rhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities. Methods We conducted a retrospective cross-sectional analysis of 145 children with PSG-diagnosed A. Outcomes included PSG parameters and obstructive apnea–hypopnea index (OAHI) during REM and non-REM. Linear multivariable models examined the joint effect of rhinitis and OSA parameters with control for potential confounders. Results Rhinitis was present in 43% of children with OSA (n = 63) but overall OAHI severity was unaffected by the presence of rhinitis. In contrast, OAHI during REM sleep in children with moderate-severe OSA was significantly increased subjects with rhinitis and OSA (44.1/hr; SE = 6.4) compared with those with OSA alone (28.2/hr; SE = 3.8). Conclusion Rhinitis is highly prevalent in children with OSA. Although OSA is not more severe in children with rhinitis, they do have a distinct OSA phenotype characterized by more REM-related OSA. Further research is needed to delineate the link between REM-sleep and the physiology of the nose during health and disease.

Validation of the Spanish Version of the Test for Respiratory and Asthma Control in Kids (TRACK) in a Population of Hispanic Preschoolers

BACKGROUNDnThere is a critical need for validation studies of questionnaires designed to assess the level of control of asthma in children younger than 5 years old.nnnOBJECTIVEnTo validate the Spanish version of the Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire in children younger than age 5 years with symptoms consistent with asthma.nnnMETHODSnIn a prospective cohort validation study, parents and/or caregivers of children younger than age 5 years and with symptoms consistent with asthma, during a baseline and a follow-up visit 2 to 6 weeks later, completed the information required to assess the content validity, criterion validity, construct validity, test-retest reliability, sensitivity to change, internal consistency reliability, and usability of the TRACK questionnaire.nnnRESULTSnMedian (interquartile range) of the TRACK scores were significantly different between patients with well-controlled asthma, patients with not well-controlled asthma, and patients with very poorly controlled asthma (90.0 [75.0-95.0], 75.0 [55.0-85.0], and 35.0 [25.0-55.0], respectively, P < .001). TRACK scores were significantly different between patients classified as currently symptomatic and symptomatic in the recent past (42.5 [25.0-55.0] vs 85.0 [75.0-90.0]; P < .001). The intraclass correlation coefficient of the measurements was 0.755 (95% CI, 0.503-1.00). All patients whose clinical status changed showed an increase of 10 or more points in TRACK score between baseline and follow-up visits. The Cronbach α was 0.77 for the questionnaire as a whole.nnnCONCLUSIONnThe Spanish version of the TRACK questionnaire has excellent sensitivity to change and usability; adequate criterion validity, construct validity, and test-retest reliability; and an acceptable internal consistency, when used in children younger than age 5 years with symptoms consistent with asthma.

Validation of the Spanish version of the childhood asthma control test (cACT) in a population of Hispanic children.

Abstract Background: There is a critical need for additional validation studies of questionnaires designed to assess the level of control of asthma in pediatric patients. Objective: To validate the Spanish version of the Childhood Asthma Control Test (cACT) in children aged between 4 and 11 years with physician-diagnosed asthma. Methods: In a prospective cohort validation study, asthmatic children aged between 4 and 11 years and their parents, attended both a baseline and a follow-up visit 2 to 6 weeks later. In these two visits, they completed the information required to assess the criterion validity, construct validity, test-retest reliability, sensitivity to change, internal consistency and usability of the cACT. Results: At baseline, cACT scores were significantly different between patients with controlled, partly controlled and uncontrolled asthma [24.0 (23.0–26.0), 18.0 (18.0–22.0), and 17.5 (13.0–20.0), respectively, pu2009<u20090.001], and also between patients for whom this visit resulted in a step-up, no change or step-down in therapy [18.0 (15.0–21.0), 24.0 (23.0–24.0) and 26.0 (23.5–26.0) respectively, pu2009<u20090.001]. The score of the cACT correlated positively and significantly with the score of the Pediatric Asthma Caregivers Quality of life Questionnaire - PACQLQ (Spearmans rhou2009=u20090.50, pu2009<u20090.001). The intraclass correlation coefficient of the measurements in patients with no change in clinical status was 0.849 (95% CI: 0.752–0.908). There were statistical significant differences between baseline and follow-up cACT scores in patients with an improvement in clinical status [19.0 (18.0–22.0) versus 24.5 (24.0–25.0), pu2009<u20090.001]. Cronbachs α was 0.8276 for the questionnaire as a whole. Conclusion: The Spanish version of the cACT has adequate criterion validity, adequate construct validity, adequate sensitivity to change, good internal consistency, good test-retest reliability and excellent usability when administered to asthmatic children aged between 4 and 11 years.

Systematic review of instruments aimed at evaluating the severity of bronchiolitis.

OBJECTIVEnNo recent studies have performed a systematic review of all available instruments aimed at evaluating the severity of bronchiolitis. The objective of the present study was to perform a systematic review of instruments aimed at evaluating the severity of bronchiolitis and to evaluate their measurement properties.nnnMETHODSnA systematic search of the literature was performed in order to identify studies in which an instrument for evaluating the severity of bronchiolitis was described. Instruments were evaluated based on their reliability, validity, utility, endorsement frequency, restrictions in range, comprehension, and lack of ambiguity.nnnRESULTSnA total of 77 articles, describing a total of 32 different instruments were included in the review. The number of items included in the instruments ranged from 2 to 26. Upon analyzing their content, respiratory rate turned out to be the most frequently used item (in 26/32, 81.3% of the instruments), followed by wheezing (in 25/32, 78.1% of the instruments). In 18 (56.3%) instruments, there was a report of at least one of their measurement properties, mainly reliability and utility. Taking into consideration the information contained in the instruments, as well as their measurement properties, one was considered to be the best one available.nnnCONCLUSIONSnAmong the 32 instruments aimed at evaluating the severity of bronchiolitis that were identified and systematically examined, one was considered to be the best one available. However, there is an urgent need to develop better instruments and to validate them in a more comprehensive and proper way.

A systematic review of instruments aimed at evaluating metered-dose inhaler administration technique in children

Abstract Objective. The objective of the present study was to perform a systematic review of instruments aimed at evaluating pressurized metered-dose inhaler (pMDI) administration technique in children and evaluating the measurement properties of these instruments. Methods. A systematic search of the literature was performed in order to identify studies in which an instrument (scale, checklist, or questionnaire) for evaluating pMDI administration technique in children was described. Instruments were evaluated based on their reliability, validity, utility, endorsement frequency, restrictions in range, comprehension, lack of ambiguity, and lack of value-laden or offensive content. Results. A total of 24 instruments were identified. The age of the children ranged from 1 month to 18 years, the number of steps or items included in the instruments ranged from 3 to 21, and nearly half of the instruments distinguished between essential and non-essential steps or items. In only 7 of the 24 instruments was there a report of their measurement properties, mainly reliability and utility. Taking into consideration the information contained in the instruments, as well as their measurement properties, we determined four instruments to be the best of the available ones. Conclusions. Among the 24 instruments for the assessment of pMDI administration technique in children that were identified and systematically examined, four were considered to be the best ones available. However, additional evaluation of their measurement properties should be done before using them in clinical practice and for research purposes.

Characterization of mucoid and serous middle ear effusions from patients with chronic otitis media: implication of different biological mechanisms?

BackgroundChronic otitis media with effusion (COME) is characterized by persistent middle ear effusions that are in most cases highly viscous, but some patients present with serous fluid. This study aimed at comprehensively characterizing the macromolecular composition of mucoid vs. serous middle ear effusions (MEEs).MethodsMEEs from patients with COME were analyzed for proteins by mass spectrometry (MS) and western blot techniques, total DNA quantity, bacterial DNA (16S sequencing), and cytokine content. Proteomics datasets were studied in Ingenuity Pathway Analysis (IPA).ResultsMucoid samples showed a global tendency of increased pro-inflammatory mediators. Interleukin-1β (IL-1β) and IL-10 were significantly more abundant in serous samples (pu2009<u20090.01). Mucoid samples had higher DNA quantity (pu2009=u20090.04), more likely to be positive in MUC5B protein (pu2009=u20090.008) and higher peptide counts (12,786 vs. 2225), as well as an overall larger number of identified proteins (331 vs. 177), compared to serous. IPA found the mucoid sample dataset to be related to immune cell function and epithelial remodeling, whereas the serous sample dataset showed acute responses and blood-related proteins. Interestingly, serous samples showed more bacterial DNA than mucoid ones, with less bacterial genera variability.ConclusionThis study demonstrates divergent immune responses in children with COME by effusion quality.

Predictors of prolonged length of hospital stay for infants with bronchiolitis

Among inpatients suffering from bronchiolitis, approximately a quarter may undergo a prolonged length of stay (LOS) for the treatment of their respiratory condition. However, there have been few research studies that have evaluated variables that may be associated with a prolonged LOS in these patients, especially in low-income and middle-income countries, where the clinical and economic burden of the disease is the greatest. In an analytical single-center cross-sectional study, we included a population of patients with acute bronchiolitis hospitalized between March and June 2016. We collected demographic and clinical information and the LOS of each patient. Prolonged LOS for bronchiolitis was defined as at least one hospital stay of 5 or more days. A total of 303 patients were included, with 176 (58.1%) male and a median (IQR) age of 3.0 (1.0–7.0) months. After controlling for gender, history of bronchopulmonary dysplasia, number of days with respiratory symptoms, the presence of apnea as an initial manifestation of bronchiolitis, and other underlying disease conditions, we found that the independent predictors of prolonged LOS for bronchiolitis in our study population included age (OR 0.92; 95% CI 0.84 to 0.99; p=0.049), history of prematurity (OR 6.34; 95% CI 1.10 to 36.46; p=0.038), respiratory syncytial virus isolation (OR 1.92; 95% CI 1.02 to 3.73; p=0.048), and initial oxygen saturation (OR 0.94; 95% CI 0.88 to 0.98; p=0.048). The factors identified should be taken into account when planning policies to reduce the duration of hospital stay in infants with bronchiolitis.

MP5: STABLE ISOTOPE LABELED BY AMINO ACID IN CULTURE (SILAC) STRATEGY TO ANALYZE HUMAN MIDDLE EAR EPITHELIAL CELLS (HMEEC) SECRETOME IN RESPONSE TO NTHI LYSATES: EVIDENCE OF THE IMPLICATION OF EXOSOMES IN OTITIS MEDIA

Purpose of Study This study aimed at characterizing the secretome of HMEEC-1 and to evaluate its regulation in response to NTHi lysates and better understand the pathogenesis of Otitis Media (OM). Methods Used HMEEC-1 were labeled with heavy isotopes of arginine and lysine to obtain a spike-in standard that was mixed with the conditions of interest (control or treated 24u2005hrs, secretions recovered 24u2005hrs or 48u2005hrs) and separated by SDS-PAGE. Peptides generated by in-gel digestion were analyzed by LC-MS/MS. Middle ear effusions (MEEs) from patients having chronic OM were analyzed to validate the results obtained with HMEEC. Summary of Results 767 proteins were detected by MS in HMEEC secretions. The more abundant proteins detected were components of the extracellular matrix, proteins implicated in the innate immune response, and surprisingly proteins implicated in the processing and packaging of RNA. These proteins were heterogenous nuclear ribonucleoproteins A2/B1 (hnRNPA2B1) and K (hnRNPK) enriched at the 24u2005hrs time point (1.99 and 1.78 fold change respectively) and Q at 48u2005hrs (hnRNPQ, fold change 4.76) in response to NTHi lysates. We then hypothesized that these proteins were implicated in the packaging of miRNAs in exosomes in response to NTHi lysates. An exosome marker assay showed the presence of exosomes in both the cell secretions and MEEs. A western blot analysis of MEE exosome proteins showed the presence of hnRNPs as in cell secretions. Finally, a Nanostring chip assay demonstrated the presence of 8 miRNA in MEEs, mostly reported to be produced by epithelial cells and neutrophils. Conclusions We characterized the secretome of HMEEC in response to NTHi lysates treatment that show a potential implication of exosomes in the pathogenesis of OM. We demonstrated the presence of exosomes in HMEEC secretions and MEEs, transporting miRNAs packaged by hnRNP proteins.