Expression of interleukin-4, interleukin-9 and interleukin-13 in peripheral blood mononuclear cells of cystic fibrosis patients with and without allergy

Bronchial hyperresponsiveness (BHR) and mucus overproduction are common in CF pulmonary disease and allergic reactions can be frequently observed in cystic fibrosis (CF) lung disease. However, the underlying pathophysiological mechanisms are far from being completely understood. Therefore the expression of the Th2 type cytokines interleukin (IL)-4, IL-9 and IL-13 in CF patients with allergy was compared to patients without allergy. Peripheral blood mononuclear cells (PBMC) samples from 9 allergic CF patients and 8 non-allergic CF patients were obtained. In situ hybridization and immunocytochemistry were performed to determine mRNA and protein expression of IL-4, IL-9, and IL-13 in PBMC. PBMC from allergic CF patients expressed significantly more IL-13 mRNA and protein compared to non-allergic patients (p < 0.05). There was no significant difference for IL-4 and IL-9 between the two groups. In both groups IL-9 mRNA and protein expression were significantly higher compared to IL-4 and IL-13 expression (p < 0.05). These results suggest that IL-13 plays an important role in allergic disease in CF. Moreover, IL-9 may be important in CF disease whether allergy is present or not as it may contribute to BHR and mucus overproduction

Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): Protocol for a multicentre randomised placebo-controlled triple-blind trial

Introduction Preschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D 3 supplementation on exacerbations requiring OCS, in preschoolers with recurrent URTI-induced asthma exacerbations. Methods and analysis This is a phase III, randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D 3 supplementation in children aged 1-5 years, with asthma triggered by URTIs and a recent history of frequent URTIs and OCS use. Children (n=865) will be recruited in the fall and early winter and followed for 7 months. They will be randomised to either the (1) intervention: two oral boluses of 100 000 international unit (IU) vitamin D 3 (3.5 months apart) with 400 IU vitamin D 3 daily; or (2) control: identical placebo boluses with daily placebo. The primary outcome is the number of exacerbations requiring OCS per child, documented by medical and pharmacy records. Secondary outcomes include number of laboratory-confirmed viral URTIs, exacerbation duration and severity, parent functional status, healthcare use, treatment deintensification, cost and safety. Ethics and dissemination This study has received ethical approval from all sites. Results will be disseminated via international conferences and manuscripts targeting paediatricians and respirologists, and to families of asthmatic children via our Quebec parents-partners outreach programme. If proven effective, findings may markedly influence the management of URTI-induced asthma in high-morbidity preschoolers and could be directly implemented into practice with an update to clinical guidelines. Trial registration number NCT03365687

Pediatric home mechanical ventilation: A Canadian Thoracic Society clinical practice guideline executive summary

Over the last 30 to 40 years, improvements in technology, as well as changing clinical practice regarding the appropriateness of long-term ventilation in patients with “non-curable” disorders, have resulted in increasing numbers of children surviving what were previously considered fatal conditions. This has come but at the expense of requiring ongoing, long-term prolonged mechanical ventilation (both invasive and noninvasive). Although there are many publications pertaining to specific aspects of home mechanical ventilation (HMV) in children, there are few comprehensive guidelines that bring together all of the current literature. In 2011 the Canadian Thoracic Society HMV Guideline Committee published a review of the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. This current document is intended to be a companion to the 2011 guidelines, concentrating on the issues that are either unique to children on HMV (individuals under 18 years of age), or where common pediatric practice diverges significantly from that employed in adults on long-term home ventilation. As with the adult guidelines,1 this document provides a disease-specific review of illnesses associated with the necessity for long-term ventilation in children, including children with chronic lung disease, spinal muscle atrophy, muscular dystrophies, kyphoscoliosis, obesity hypoventilation syndrome, and central hypoventilation syndromes. It also covers important common themes such as airway clearance, the ethics of initiation of long-term ventilation in individuals unable to give consent, the process of transition to home and to adult centers, and the impact, both financial, as well as social, that this may have on the child\u27s families and caregivers. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information

Toll Like Receptors 4 and 2 Expression in the Bronchial Mucosa of Patients with Cystic Fibrosis

BACKGROUND: Cystic fibrosis (CF) is a lung disease characterized by chronic infection with Gram-negative bacteria Pseudomonas aeruginosa and Gram-positive bacteria Staphylococcus aureus. Recently, toll-like receptor (TLR) 4 has been shown to be responsible for the lipopolysaccharide (LPS)-mediated immune response. While TLR2 mediates responses driven by bacterial lipoproteins and peptidoglycans from Gram-positive bacteria, LPS derived from P aeruginosa may stimulate the immune response in the airways of patients with CF via activation of TLR4

Niflumic acid and MSI-2216 reduce TNF-α–induced mucin expression in human airway mucosa

Human chloride channel, calcium-activated 1 (hCLCA1) has been shown to induce mucin (MUC) gene expression and mucus production in bronchial epithelial cells. To investigate whether blocking hCLCA1 decreases mucus production. Expression of hCLCA1 and mucus was stimulated with TNF-α in human upper airway mucosal explant tissue. MUC5AC mRNA and mucus protein expression was blocked by inhibiting hCLCA1 by using channel blockers (niflumic acid [NFA] and MSI-2216) without and with TNF-α stimulation. Expression of MUC5AC, hCLCA1, and COX-2 mRNA was quantified by using real-time PCR. Mucus protein was assessed by periodic acid Schiff staining. Laser capture microdissection was performed to quantify hCLCA1 and MUC5AC mRNA expression in epithelial cells derived from mucosal explant tissue. TNF-α significantly increased MUC5AC and hCLCA1 mRNA as well as mucus and hCLCA1 protein expression in the mucosal explant tissue ( P < .05). Inhibition of hCLCA1 with NFA or MSI-2216 showed a significant dose-dependent reduction of mucus production for both blockers in the mucosal explant tissue ( P < .05). MUC5AC mRNA was also decreased by both blockers in the whole mucosal tissue and in laser-captured mucosa epithelial cells. Unstimulated and TNF-α–induced mucin expression could be decreased by NFA and MSI-2216. Inhibiting hCLCA1 may be a potential new approach to reduce mucus overproduction