BACKGROUND. The lipid-laden macrophage index has been used to evaluate for gastroesophageal reflux-related respiratory disease, but the relationship between reflux detected by pH probe and the lipid-laden macrophage index is uncertain despite widespread use of the lipid-laden macrophage index in clinical decision-making. It was the aim of this study to correlate reflux as detected by multichannel intraluminal impedance with the lipid-laden macrophage index.
METHODS. Patients undergoing both pH multichannel intraluminal impedance testing and bronchoscopy between January 2002 and January 2006 were identified. Baseline characteristics were compared by using parametric and nonparametric testing. Reflux profiles were correlated with the lipid-laden macrophage index by using Spearman correlations.
RESULTS. There was no significant correlation between the lipid-laden macrophage index and the number of acid or nonacid reflux events. There also was no significant correlation between the lipid-laden macrophage index and the amount of full- column reflux. There was no significant difference between the mean lipid-laden macrophage index in patients with and without esophagitis. Finally, in patients who underwent fundoplication (n = 13) for intractable respiratory disease, there was no significant difference in any of the reflux parameters between patients who did and did not experience clinical improvement after fundoplication. There was, however, a higher lipid-laden macrophage index in patients with no symptomatic improvement compared with patients with symptomatic improvement.
CONCLUSIONS. Lipid-laden macrophage index lacks the specificity necessary to detect reflux-related respiratory disease.
A 7-month-old-term male infant presented with cough, tachypnoea, hypoxaemia and post-tussive emesis. Clinical history was significant for respiratory failure and pulmonary hypertension in the neonatal period requiring assisted ventilation, congenital hypothyroidism, mild hypotonia, recurrent respiratory infections, hypoxaemia requiring supplemental oxygen and nasogastric tube feeds. Physical examination showed tachypnoea, coarse bilateral breath sounds and mild hypotonia. Chest radiograph revealed multifocal pulmonary opacities with coarse interstitial markings and right upper lobe atelectasis. Following antibiotic therapy for suspected aspiration pneumonia, chest CT scan was performed and showed multiple areas of pulmonary consolidation and scattered areas of bilateral ground-glass opacities. Genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene consistent with a diagnosis of brain-thyroid-lung (BTL) syndrome. Our case highlights the importance of genetic studies to diagnose BTL syndrome in infants with hypothyroidism, hypotonia and lung disease.
Rationale
Airway thiol redox disturbances, including depletion of the antioxidant, glutathione (GSH), are differentiating features of severe asthma in children.
Objectives
Given the role of the transcription factor, Nrf2, in maintaining GSH homeostasis and antioxidant defense, we quantified expression and activity of Nrf2 and its downstream targets in the airways and systemic circulation of asthmatic children. We hypothesized that Nrf2 activation and function would be impaired in severe asthma, resulting in depletion of thiol pools and insufficient GSH synthesis and conjugation.
Methods
Peripheral blood mononuclear cells (PBMCs) and airway lavage cells were collected from children 6–17 years with severe (n=51) and mild-to-moderate asthma (n=38). The thiols GSH and cysteine (CyS) were quantified and expression and activity of Nrf2 and its downstream targets were assessed.
Results
Children with severe asthma had greater oxidation and lower concentrations of GSH and Cys in the plasma and airway lavage. Although Nrf2 mRNA and protein increased in severe asthma as a function of increased thiol oxidation, the Nrf2 expressed was highly dysfunctional. Nrf2 activation and downstream targets of Nrf2 binding, including GSH-dependent enzymes, were not different between groups. The duration of asthma was a key factor associated with Nrf2 dysfunction in severe asthma.
Conclusions
Children with severe asthma have a global disruption of thiol redox signaling and control in both the airways and systemic circulation that is associated with post-translational modification of Nrf2. We conclude that the Nrf2 pathway is disrupted in severe asthma as a function of chronic oxidative stress, which ultimately inhibits GSH synthesis and antioxidant defense.
Objective: To describe clinical factors associated with mortality and causes of death in tracheostomy-dependent (TD) children.
Methods: A retrospective study of patients with a new or established tracheostomy requiring hospitalization at a large tertiary children's hospital between 2009 and 2015 was conducted. Patient groups were developed based on indication for tracheostomy: pulmonary, anatomic/airway obstruction, and neurologic causes. The outcome measures were overall mortality rate, mortality risk factors, and causes of death.
Results: A total of 187 patients were identified as TD with complete data available for 164 patients. Primary indications for tracheostomy included pulmonary (40%), anatomic/airway obstruction (36%), and neurologic (24%). The median age at tracheostomy and duration of follow up were 6.6 months (IQR 3.5–19.5 months) and 23.8 months (IQR 9.9–46.7 months), respectively. Overall, 45 (27%) patients died during the study period and the median time to death following tracheostomy was 9.8 months (IQR 6.1–29.7 months). Overall survival at 1- and 5-years following tracheostomy was 83% (95% CI: 76–88%) and 68% (95% CI: 57–76%), respectively. There was no significant difference in mortality based on indication for tracheostomy (p = 0.35), however pulmonary indication for tracheostomy was associated with a shorter time to death (HR: 1.9; 95% CI: 1.04–3.4; p = 0.04). Among the co-morbid medical conditions, children with seizure disorder had higher mortality (p = 0.04).
Conclusion: In this study, TD children had a high mortality rate with no significant difference in mortality based on indication for tracheostomy. Pulmonary indication for tracheostomy was associated with a shorter time to death and neurologic indication was associated with lower decannulation rates.