RESUMEN
UNLABELLED: Pulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by Veillonella and Streptococcus. Bacterial diversity increased significantly over time, with evidence of more rapidly acquired diversity in the respiratory tract. There was a high degree of concordance between the bacteria that were increasing or decreasing over time in both compartments; in particular, a significant proportion (14/16 genera) increasing in the gut were also increasing in the respiratory tract. For 7 genera, gut colonization presages their appearance in the respiratory tract. Clustering analysis of respiratory samples indicated profiles of bacteria associated with breast-feeding, and for gut samples, introduction of solid foods even after adjustment for the time at which the sample was collected. Furthermore, changes in diet also result in altered respiratory microflora, suggesting a link between nutrition and development of microbial communities in the respiratory tract. Our findings suggest that nutritional factors and gut colonization patterns are determinants of the microbial development of respiratory tract microbiota in infants with CF and present opportunities for early intervention in CF with altered dietary or probiotic strategies. IMPORTANCE: While efforts have been focused on assessing the microbiome of pediatric and adult cystic fibrosis (CF) patients to understand how chronic colonization by these microbes contributes to pulmonary damage, little is known regarding the earliest development of respiratory and gut microflora in infants with CF. Our findings suggest that colonization of the respiratory tract by microbes is presaged by colonization of the gut and demonstrated a role of nutrition in development of the respiratory microflora. Thus, targeted dietary or probiotic strategies may be an effective means to change the course of the colonization of the CF lung and thereby improve patient outcomes.
Asunto(s)
Biota , Fibrosis Quística/microbiología , Tracto Gastrointestinal/microbiología , Metagenoma , Sistema Respiratorio/microbiología , Factores de Edad , Bacterias/clasificación , Bacterias/genética , Análisis por Conglomerados , Humanos , Lactante , Recién NacidoRESUMEN
AIM: The goal of this study was to understand whether dense fibrillar collagen matrices, with a hierarchical structure resembling native collagen matrices, could be useful to study collagen receptor function, in a more physiological context. The receptor analysed here was integrin α11ß1, already shown to be involved in cell attachment and migration on collagen-coated plastic, and also in contraction of loose fibrillar collagen hydrogels. MATERIALS AND METHODS: Collagen matrices prepared here corresponded to dense fibrillar hydrogels concentrated at 5mg/ml. The behaviour of α11ß1 deficient fibroblasts seeded on these concentrated matrices was assessed in terms of adhesion, morphology and migration, then compared to that observed on classical hydrogels at 1mg/ml, corresponding to loose collagen matrices. RESULTS: Short-term attachment assays showed disturbed interactions between α11ß1 deficient cells and collagen matrices in a concentration-dependent manner. Long-term assays revealed reduced cell spreading of alpha 11(-/-) cells on the dense collagen matrices, associated with a disturbed cytoskeleton network. Moreover, anoikis was observed when alpha 11(-/-) cells were seeded on 5mg/ml matrices, and not on looser 1mg/ml matrices. In scratch wound in vitro assays, carried out with cells on 5mg/ml fibrillar collagen matrices, alpha 11(-/-) cells migrated much better than their wild-type counterparts. In contrast, no significant difference was observed between wild and knock-out cells seeded on plastic. CONCLUSIONS: The present study demonstrates the validity of in vivo-like dense fibrillar collagen matrices to evaluate cell receptor functions more significantly than with 2D cell cultures or loose hydrogels.
Asunto(s)
Matriz Extracelular/metabolismo , Colágenos Fibrilares/farmacología , Receptores de Superficie Celular/fisiología , Animales , Animales Recién Nacidos , Adhesión Celular/efectos de los fármacos , Adhesión Celular/genética , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Células Cultivadas , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Dermis/fisiología , Embrión de Mamíferos , Matriz Extracelular/genética , Matriz Extracelular/fisiología , Matriz Extracelular/ultraestructura , Colágenos Fibrilares/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/fisiología , Integrinas/genética , Integrinas/metabolismo , Integrinas/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores de Colágeno/genética , Receptores de Colágeno/metabolismo , Receptores de Colágeno/fisiologíaRESUMEN
A study involving eight children with moderate persistent asthma was undertaken to determine whether standard swimming lessons improved symptoms and pulmonary function tests (PFTs) in asthmatic children. Five children ages 7-12 years old with moderate persistent asthma were randomized to a swimming lesson group (5- to 6-week session) and three to a control group. Both groups completed pre- and poststudy period PFTs and symptom questionnaires. Swimming lessons did not produce a significant change in asthma symptoms or PFTs. Review of previous literature found that swimming has been shown to have definite benefits in improving cardiorespiratory fitness in asthmatic children. Swimming has been shown to be less asthmogenic than other forms of exercise. Some studies have also shown improvement in asthma symptoms in children participating in exercise programs.
Asunto(s)
Asma/terapia , Terapia por Ejercicio , Natación/fisiología , Asma/diagnóstico , Asma/fisiopatología , Asma Inducida por Ejercicio/fisiopatología , Niño , Terapia por Ejercicio/métodos , Femenino , Humanos , Masculino , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: Gastroesophageal reflux (GER) occurs frequently in infants and children and is implicated as a trigger for reactive airways disease. While evaluating patients for GER by upper gastrointestinal studies (UGI), we frequently noticed laryngeal penetration or tracheal aspiration in infants < 1 year of age. We conducted this prospective study to assess the incidence of swallowing dysfunction in infants with vomiting or respiratory symptoms. METHODS: Between February 1994 and August 1997, 1,003 UGI in infants < 1 year of age were performed by two experienced pediatric radiologists. Fluoroscopy of swallowing using an appropriate image intensifier was observed as part of the UGI in all patients. In addition to evaluating premature infants, former premature infants, and infants with underlying conditions such as bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), esophageal atresia and/or tracheoesophageal fistula (EA), and neurologic disorders, we assessed swallowing in 472 full-term infants in the general population who had respiratory symptoms or suspected GER, but no other apparent abnormalities. Swallowing was not assessed in patients with congenital bowel obstruction. The presence of normal swallowing or swallowing dysfunction was recorded immediately following the study. Chest radiographs obtained on the same day as the UGI were evaluated in the study. Forty-four videotaped modified barium-swallow studies (MBSS) were obtained in 25 general-population infants and reviewed frame-by-frame to determine the length of time that barium could be visualized in the subglottic trachea. RESULTS: The incidence of swallowing dysfunction is significant in premature and former premature infants, those with BPD, CHD, EA, various syndromes, and neurologic abnormality. In the general population of full-term infants referred for evaluation of vomiting or respiratory symptoms, 63 (13.4 % of 472) had swallowing dysfunction. Forty-four had tracheal aspiration (TA) and 19 had laryngeal penetration (LP). Gastroesophageal reflux was found in 79.5 % with TA and in 68.4 % with LP. The MBSS confirmed swallowing dysfunction in all patients shown to have vocal cord penetration or tracheal aspiration by UGI. CONCLUSIONS: Careful evaluation of swallowing during an UGI can identify swallowing dysfunction in full-term infants who have respiratory problems, as well as in infants with an abnormality that predisposes the patient to aspiration. Episodes of tracheal aspiration may be fleeting and overlooked if swallowing is not assessed carefully. An MBSS can confirm the observation of swallowing dysfunction found during an UGI and assist in planning appropriate dietary therapy that minimizes the likelihood of tracheal aspiration during feeding.
Asunto(s)
Trastornos de Deglución , Trastornos de Deglución/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: The goal was to determine whether decannulation can be safely achieved in children with persistent oxygen requirements. DESIGN: The study was a prospective evaluation of 12 oxygen-dependent children at a tertiary care academic children's medical center. METHODS: Twelve tracheotomy-dependent children with persistent oxygen requirements were evaluated for decannulation. Patients requiring more than 35% FiO(2) were not considered. Direct laryngoscopy and bronchoscopy were performed in all patients. Two required single-stage laryngotracheoplasty to correct subglottic stenosis, 1 required tracheal resection, and 7 required removal of suprastomal granulation tissue. Oxygen was administered after decannulation through a nasal cannula. RESULTS: Decannulation was successful in 92% (11 of 12) of patients. At final follow-up, oxygen requirements decreased in 58% of patients after decannulation. CONCLUSIONS: Decannulation can be successful in children who remain oxygen dependent; conversion to a more physiologic airway may be an adjunct to reducing or eliminating their oxygen demand.
Asunto(s)
Displasia Broncopulmonar/cirugía , Respiración Artificial , Traqueotomía , Enfermedad Crónica , Comorbilidad , Femenino , Tejido de Granulación/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: To determine the benefit of nasally inhaled dornase alfa in cystic fibrosis (CF) sinusitis. DESIGN: Retrospective chart review comparing postsurgical course, radiographic studies, and pulmonary function test results in patients who were treated with nasally inhaled dornase alfa with those in patients who were not treated with dornase alfa. PATIENTS: Twenty consecutive patients with CF who underwent functional endoscopic sinus surgery from 1993 to 1997 were included in the study. Treatment with nasally inhaled dornase alfa was initiated in 5 of the 20 patients after they underwent functional endoscopic sinus surgery. SETTING: Tertiary care academic center. RESULTS: The dornase alfa-treated patients had less mucosal edema and no polyps at serial endoscopy over 3 years compared with the non-dornase alfa-treated patients. The patients who received nasally inhaled dornase alfa also underwent fewer revision functional endoscopic sinus surgical procedures (1.6 vs 3.2), even though there was essentially no change in pulmonary function test results in these patients. CONCLUSIONS: Sinusitis continues to be a major cause of morbidity in patients with CF. Symptomatic patients frequently require multiple drug regimens, including long-term systemic antibiotic therapy, topical and systemic steroid therapy, and antibiotic nasal irrigations. This preliminary study indicates the potential impact of nasally inhaled dornase alfa in controlling postoperative symptoms in CF sinusitis.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasa I/administración & dosificación , Expectorantes/administración & dosificación , Pólipos Nasales/cirugía , Complicaciones Posoperatorias/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Administración por Inhalación , Adolescente , Adulto , Niño , Enfermedad Crónica , Endoscopía , Femenino , Humanos , Masculino , Proteínas Recombinantes/administración & dosificación , Estudios RetrospectivosAsunto(s)
Fibrosis Quística/genética , Enfermedades Pulmonares/etiología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Fibrosis Quística/complicaciones , Fibrosis Quística/mortalidad , Fibrosis Quística/terapia , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades Pulmonares/diagnóstico , Masculino , Factores de Riesgo , Tasa de Supervivencia , Vitaminas/uso terapéuticoRESUMEN
The DiGeorge syndrome has been associated with various immune deficits. Embryologically, defects of the neural crest are associated with conotruncal and aortic arch abnormalities. The objective of this study was to determine if children with neural crest congenital heart defects can have subtle but significant immunodeficiencies. Complete blood counts with differential counts and a standard lymphocyte immunophenotyping panel of selected monoclonal antibodies were performed on peripheral blood from 20 children with neural crest cardiac disease and 34 normal newborns. The children with cardiac disease were grouped as survivors and nonsurvivors. The mean total white blood cell count was similar for all groups, but the percent lymphocytes was significantly less in the nonsurvivors than in the survivors and normal newborns (p < 0. 02). The lymphocyte subsets affected were CD2, CD3, and CD4. When the cardiac patients were compared to the normal newborns, again differences in lymphocyte subsets CD2, CD3, and CD4 were seen. When comparing nonsurvivors with survivors, the mean percentages of the CD2, CD3, and CD4 T lymphocyte markers, as well as the mean lymphocyte, B cell (CD20), and natural killer cell (CD16) percentages were all lower in the nonsurvivors. It was concluded that abnormalities in specific lymphocyte populations and their subsets may be predictors of infants at greatest risk for immunodeficiency complications. Therefore children with neural crest cardiac defects should have evaluations of lymphocyte subsets at birth and be treated as if potentially immunodeficient.
Asunto(s)
Linfocitos B/inmunología , Cardiopatías Congénitas/inmunología , Cresta Neural/anomalías , Linfocitos T/inmunología , Anticuerpos Monoclonales , Síndrome de DiGeorge/sangre , Síndrome de DiGeorge/complicaciones , Síndrome de DiGeorge/inmunología , Femenino , Citometría de Flujo , Estudios de Seguimiento , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/mortalidad , Humanos , Inmunofenotipificación , Lactante , Recién Nacido , Recuento de Linfocitos , Masculino , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Asma Inducida por Ejercicio , Agonistas Adrenérgicos beta/uso terapéutico , Albuterol/análogos & derivados , Albuterol/uso terapéutico , Antiasmáticos/uso terapéutico , Asma Inducida por Ejercicio/diagnóstico , Asma Inducida por Ejercicio/tratamiento farmacológico , Asma Inducida por Ejercicio/fisiopatología , Broncodilatadores/uso terapéutico , Niño , Cromolin Sódico/uso terapéutico , Humanos , Aptitud Física , Xinafoato de SalmeterolRESUMEN
Gastroesophageal reflux is often overlooked as both a cause and a complication of respiratory disease in children. The manifestations may be protean and may bear little clinical relationship to the gastrointestinal tract. However, a high index of suspicion for its potential role in unexplained respiratory symptoms may yield large benefits for the physician and patient alike.
Asunto(s)
Asma/etiología , Reflujo Gastroesofágico/complicaciones , Enfermedades Respiratorias/etiología , Asma/complicaciones , Asma/diagnóstico , Niño , Unión Esofagogástrica/fisiopatología , Femenino , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Humanos , Lactante , Recién Nacido , Masculino , Enfermedades Respiratorias/complicaciones , Enfermedades Respiratorias/diagnósticoAsunto(s)
Asma/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , LactanteRESUMEN
Optimal management of asthma in children requires a program of patient education, avoidance of triggers, prevention of airway inflammation, and symptomatic management of episodic wheezing. Use of patient-initiated interventions based on peak expiratory flow rates determined daily in the home setting promotes early interruption of symptom cycles and better assessment of severity of disease. A fully outlined management program for any given patient requires investment of time and energy on the part of the physician, but the long term rewards for both physician and patient are significant.
Asunto(s)
Asma/tratamiento farmacológico , Asma/clasificación , Asma/fisiopatología , Niño , HumanosRESUMEN
Exercise challenges were performed on 166 middle and high school student athletes (aged 12 to 18 years) to evaluate undiagnosed exercise-induced asthma (EIA). Seventy-three percent were male, 70% were white, and 30% were black. All students completed a questionnaire and were briefly interviewed to elicit risk factors for EIA. Resting spirometry, exercise treadmill provocation, and postexercise spirometry at 1, 10, 20, and 30 minutes were performed. Twenty-two students had reductions in FEV1 > or = 15% from baseline; 15 of these had FEV1 reductions > or = 20%. Of students considered at risk for EIA by history or baseline spirometry (N = 48, 29%) eight (17%) demonstrated EIA after exercise. Of students with no risk factors (N = 118, 71%), 14 (12%) demonstrated EIA after exercise, but would not have been identified without exercise challenge. The overall incidence of EIA was 12%, a rate that is consistent with previous studies of college and Olympic athletes. Sixty-four percent of students identified with EIA were not considered at risk by routine screening methods. History and spirometry alone may not be adequate as screening tools for EIA in adolescents.
Asunto(s)
Asma Inducida por Ejercicio/epidemiología , Asma Inducida por Ejercicio/prevención & control , Tamizaje Masivo , Deportes , Adolescente , Niño , Femenino , Humanos , Masculino , Factores de Riesgo , Espirometría , Encuestas y CuestionariosRESUMEN
REPORT OF A CASE: A 21-year-old black man presented to the dermatology clinic with a complaint of redness and swelling of the lateral aspect of his right lower eyelid that progressed to the left lower eyelid. These symptoms were exacerbated by exposure to sunlight. Physical examination revealed erythematous plaques with areas of hair loss and scarring of the lower eyelids (Figs 1 and 2). Results of initial laboratory examinations were significant for the following: antinuclear antibody titer, 1:80 (in a speckled pattern), and a normal angiotensin-converting enzyme concentration. The chest roentgenogram was normal. A biopsy specimen of the right lower eyelid was obtained for routine histologic studies (Figs 3 and 4) and direct immunofluorescence (Fig 5). What is your diagnosis? DIAGNOSIS: Discoid lupus erythematosus (DLE). HISTOPATHOLOGIC FINDINGS: The biopsy specimen of the right lower eyelid initially revealed mild-to-moderate chronic inflammatory changes with a patchy lymphohistiocytic infiltrate in a perivascular.
RESUMEN
OBJECTIVE--As part of their preparticipation physical examinations, 1241 middle and high school student athletes completed a questionnaire and were interviewed to elicit risk factors for unrecognized exercise-induced bronchospasm (EIB). Spirometry was then performed when the students were at rest. RESEARCH DESIGN--All participants completed a questionnaire, were interviewed, and underwent baseline testing to determine forced expiratory volume in 1 second (FEV1). SETTING--All testing was performed in a school setting. SELECTION PROCEDURES--Athletes known to have EIB who were receiving appropriate treatment (46 athletes [4%]) and athletes with no risk factors based on medical history and normal results of spirometry (847 athletes [68%]) were eliminated from further evaluation. Students with medical histories indicating risk of unrecognized EIB and students with abnormal results of spirometry were eligible for exercise challenge by standard treadmill protocol. MEASUREMENTS AND RESULTS--Of the 348 eligible students, 230 (66%) completed the exercise challenge. Sixty-six of the 230 students had greater than 15% reduction in FEV1, and 50 of the 66 students had greater than 20% reduction, representing a 29% occurrence of previously undiagnosed EIB in a population of students identified with screening to be at risk of unrecognized EIB. Of the 179 students identified to be at risk based on medical history only, 28% had EIB. Of 33 students with positive results of spirometry but no medical history that put them at risk, 15% had EIB. Of the 18 students with medical histories that put them at risk and positive results of spirometry, 61% had EIB. Including the subpopulation with reduction in FEV1 of greater than 15%, students shown to be at risk after screening, and students previously identified as having EIB, 145 students were identified as having EIB (12%). CONCLUSIONS--These data are in accord with results of previously reported studies of college and Olympic athletes. The data may have implications for more extensive screening in the adolescent population.