Tracheomalacia in bronchopulmonary dysplasia: Trachealis hyper-relaxant responses to S-nitrosoglutathione in a hyperoxic murine model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) with airway hyperreactivity is a long-term pulmonary complication of prematurity. The endogenous nonadrenergic, noncholinergic signaling molecule, S-nitrosoglutathione (GSNO) and its catabolism by GSNO reductase (GSNOR) modulate airway reactivity. Tracheomalacia is a major, underinvestigated complication of BPD. We studied trachealis, left main bronchus (LB), and intrapulmonary bronchiolar (IPB) relaxant responses to GSNO in a murine hyperoxic BPD model. METHODS: Wild-type (WT) or GSNOR knockout (KO) newborn mice were raised in 60% (BPD) or 21% (control) oxygen during the first 3 weeks of life. After room air recovery, adult trachealis, LB, and IPB smooth muscle relaxant responses to GSNO (after methacholine preconstriction) were studied using wire myographs. Studies were repeated after GSNOR inhibitor (GSNORi) pretreatment and in KO mice. RESULTS: GSNO relaxed all airway preparations. GSNO relaxed WT BPD trachealis substantially more than WT controls (P < .05). Pharmacologic or genetic ablation of GSNOR abolished the exaggerated BPD tracheal relaxation to GSNO and also augmented BPD IPB relaxation to GSNO. LB ring contractility was not significantly different between groups or conditions. Additionally, GSNORi treatment induced relaxation of WT IPBs but not trachealis or LB. CONCLUSION: GSNO dramatically relaxed the trachealis in our BPD model, an effect paradoxically reversed by loss of GSNOR. Conversely, GSNOR inhibition augmented IBP relaxation. These data suggest that GSNOR inhibition could benefit both the BPD trachealis and distal airways, restoring relaxant responses to those of room air controls. Because therapeutic options are limited in this high-risk population, future studies of GSNOR inhibition are needed.

Traqueomalacia en paciente con amiloidosis traqueobronquial / Tracheomalacia in a patient with tracheobronchial amyloidosis

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Interventions for primary (intrinsic) tracheomalacia in children.

BACKGROUND: Tracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnoea to common respiratory symptoms such as chronic cough and wheeze. Current practice following diagnosis of tracheomalacia includes medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP), and surgical approaches aimed at improving the calibre of the airway (airway stenting, aortopexy, tracheopexy). OBJECTIVES: To evaluate the efficacy of medical and surgical therapies for children with intrinsic (primary) tracheomalacia. SEARCH METHODS: The Cochrane Airways Group searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Group's Specialised Register, MEDLINE and EMBASE databases. The Cochrane Airways Group performed the latest searches in March 2012. SELECTION CRITERIA: All randomised controlled trials (RCTs) of therapies related to symptoms associated with primary or intrinsic tracheomalacia. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from the included study independently and resolved disagreements by consensus. MAIN RESULTS: We included one RCT that compared nebulised recombinant human deoxyribonuclease (rhDNase) with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analysed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17 to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline was also better in the placebo group compared to those on nebulised rhDNase, but the difference between groups was not statistically significant (MD 0.70; 95% CI -0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum scores, and lung function tests at two weeks also favoured placebo over nebulised rhDNase but did not reach levels of significance. AUTHORS' CONCLUSIONS: There is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulised rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.