Harry Lindahl

Longitudinal Follow-up of Bronchial Inflammation, Respiratory Symptoms, and Pulmonary Function in Adolescents after Repair of Esophageal Atresia with Tracheoesophageal Fistula

OBJECTIVEnTo characterize symptoms, pulmonary function tests (PFT) and bronchial responsiveness (BR) in adolescents after repaired esophageal atresia with tracheoesophageal fistula and correlate these with endobronchial biopsy findings.nnnSTUDY DESIGNnAfter a primary operation, 31 patients underwent endoscopies and bronchoscopies at the age of <3, 3 to 7, and >7 years. A questionnaire on respiratory and esophageal symptoms was sent to patients at a mean age of 13.7 years (range, 9.7-19.4). The questionnaire was completed by 27 of 31 patients (87%), and 25 of the 31 patients (81%) underwent clinical examination and pulmonary functioning tests. Endobronchial biopsies were analyzed for reticular basement membrane (RBM) thickness and inflammatory cells.nnnRESULTSnThe prevalence of current respiratory and esophageal symptoms was 41% and 44%, respectively. Doctor-diagnosed asthma was present in 22% of patients. A restrictive and obstructive spirometric defect was observed in 32% and 30% of patients, respectively. Increased bronchial responsiveness, detected in 24% of patients, was weakly associated with current respiratory symptoms and low forced vital capacity. Mean exhaled nitric oxide was within predicted range. RBM thickness increased slightly with age, whereas inflammatory cell counts varied from normal to moderate, with intraindividual variation.nnnCONCLUSIONnInflammation of the airways in adolescents with a history of tracheoesophageal fistula, even in the presence of atopy, does not lead, in most cases, to the type of chronic inflammation and RBM changes seen in asthma.

Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years

Background Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3u2005years. Methods 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist childrens hospital for recurrent lower respiratory symptoms at a mean age of 1u2005year were followed up at 3u2005years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12u2005months preceding the follow-up visit. Results 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and β agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3u2005years (p=0.003 and p=0.018, respectively). Conclusions Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3u2005years in this highly selected group of children.

Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age

Background: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3+ Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways. Methods: Immunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants, 4–23 months of age, under investigation for airway disease. Results: A well developed HLA-DR+ network of APC was present in all samples, approximately 50% of the cells being CD68+ macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR+ cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of APC subsets and clinical parameters, only the number of intraepithelial CD1a+ dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3+ Treg were located primarily within these isolated lymphoid follicles. Conclusion: A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Treg suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy.

Gastroesophageal Reflux in Children With a Congenital Abdominal Wall Defect

BACKGROUND/PURPOSEnGastroesophageal reflux (GER) is considered common in patients with congenital abdominal wall defects (CAWD). The aim of this study was to find out the frequency of GER in children with CAWD and, in particular, whether there is difference between patients with omphalocele and gastroschisis.nnnMETHODSnForty-two children, 19 with gastroschisis and 23 with omphalocele were examined for GER at the median age of 12.0 months (range, 1 to 132). Esophagoduodenoscopy with biopsies was performed on all patients. Eighteen patients underwent 18-hour esophageal pH-monitoring.nnnRESULTSnGER was detected in 13 patients. All but one patient of the 13 had either macroscopic or microscopic esophagitis. One patient had pathological pH monitoring only. In children with omphalocele, the incidence of GER was 43% (10 of 23), whereas in gastroschisis patients the incidence was 16% (3 of 19), (P value, not significant). The median age of omphalocele patients with GER was significantly lower (7 months) than the median age of those without GER (72 months; P = .01). In patients with gastroschisis age made no difference. Six of 32 patients (19%) with primary fascial closure (small defects) had GER, whereas 7 of 10 patients (70%) in which primary fascial closure was impossible (large defects) had GER (P < .01).nnnCONCLUSIONnCAWD patients, especially those with omphalocele and a large defect have a high incidence of GER complicated by esophagitis during the first few years of life.

Bronchoscopy during the first month of life

During the 6-year period from 1984 to 1989, 196 bronchoscopies were performed on 132 neonates. The indications were grouped into four categories: (1) difficulties in artificial ventilation or failure to wean the baby from the ventilator (52); (2) other respiratory difficulties (52); (3) audible stridor (16); and (4) routine preoperative or postoperative examination of esophageal atresia patients (12). The most common finding was laryngomalacia or tracheomalacia (31). Other findings were: obstructing tracheal or bronchial granulation or stricture (23), obstructing mucous plug (22), grave tracheobronchitis (11), tracheoesophageal H-fistula (5), laryngeal perforation (3), congenital laryngeal stenosis (2), and complete laryngotracheoesophageal cleft (1). Four patients had miscellaneous pathology. The findings were normal in 30 patients. A therapeutic procedure was included in 99 of the 196 bronchoscopies. Seven serious complications occurred during the operative bronchoscopies, two of them requiring immediate pulmonary surgery. All complications were successfully managed. In contrast, no complications occurred in the 97 purely diagnostic bronchoscopies. In experienced hands, bronchoscopy of the newborn is a safe and useful examination. Complications occur when therapeutic procedures are included. Therefore, operative bronchoscopy should only be performed in conditions in which immediate thoracotomy and pulmonary surgery can be performed.

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years

BACKGROUNDnAssociations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear.nnnOBJECTIVEnTo report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes.nnnMETHODSnFifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children.nnnRESULTSnForty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age.nnnCONCLUSIONnThe lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

Does tidal exhaled nitric oxide reflect mucosal airway inflammation in infants

Exhaled nitric oxide (FENO) has been proposed as a surrogate of airway inflammation in asthma. The measurement of FENO may be important to distinguish conditions characterised by eosinophilic inflammation from those which are non-eosinophilic, the former being more likely to respond to steroid treatment. Studies in adults and school-aged children have shown that FENO levels correlate to some extent with airway mucosal eosinophilia quantified in endobronchial biopsies.1 2 However, no such studies exist in infants. In this observational study, we assessed whether infants with recurrent respiratory symptoms, in whom bronchoscopy had been undertaken for clinical evaluation, showed evidence of a relationship between mucosal airway inflammation quantified in endobronchial biopsies and levels of FENO measured during tidal breathing.nnThe study consisted of 36 infants, aged between 3.4 and 25.9u2005months, referred for clinical evaluation of …

Results of gastric tube esophagoplasty in esophageal atresia

During the 11-year period 1975–1985, 20 gastric tube reconstructions were performed on patients with esophageal atresia. Ten had one or several associated anomalies; in 6 these were life-threatening or severe. The indications for replacement were: long gap in 12 patients, anastomotic leakage in 6, and failed colon interposition in 2. All reconstructions were made in two phases with antiperistaltic retrosternal tubes. There was no hospital mortality, but 2 tubes failed due to gross anastomotic insufficiency after the second phase. In addition, a third patient had a severe anastomotic leakage, which meant that the anastomosis had to be temporarily abandoned, a successful reanastomosis was later performed. Minor leakage occurred after the anastomosis in 8 patients, resulting in a cervical fistula in 7 and mediastinitis in 1. All complications resolved with conservative treatment. All successfully operated patients have had continuous follow-up for 2–12 years (mean 6 years). There was one late death in a patient who also had high anal atresia and died of an occlusive ileus 2 years after a Kiesewetter pull-through operation. Late complications included 5 anastomotic strictures 2 of which required resection and 3 that required prolonged dilatations. One anastomosis was perforated during routine dilatation, but was saved after two reoperations. Two patients had swallowed foreign bodies that required endoscopic removal. The subjective result, according to the criteria of Desjardins et al, was excellent in 7 patients and good in 10. All but 1 patient were within 2 standard deviations of height and weight of normal Finnish children at last measurement.

Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms

BackgroundFew data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies.MethodsThirty-nine infants (median age 0.9xa0years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies.ResultsThe differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1β, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine.ConclusionsA positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.

Prenatal muscle relaxation in congenital diaphragmatic hernia

An infant with congenital diaphragmatic hernia was given 2 mg vecuronium bromide intramuscularly in utero 40 min before vaginal delivery at 40 weeks gestation. At birth the infant had complete muscle relaxation, which facilitated decompression of the bowel and surgical correction. Prenatal muscle relaxation may improve the care of infants with congenital diaphragmatic hernia