Decorin (Dcn) is an extracellular matrix proteoglycan, which affects airway mechanics, airway-parenchymal interdependence, airway smooth muscle proliferation and apoptosis, and transforming growth factor-β bioavailability. As Dcn deposition is differentially altered in asthma, we questioned whether Dcn deficiency would impact the development of allergen-induced asthma in a mouse model. Dcn(-/-) and Dcn(+/+) mice (C57Bl/6) were sensitized with ovalbumin (OA) and challenged intranasally 3 days/wk × 3 wk. After OA challenge, mice were anesthetized, and respiratory mechanics measured under baseline conditions and after delivery of increasing concentrations of methacholine aerosol. Complex impedance was partitioned into airway resistance and tissue elastance and damping. Bronchoalveolar lavage was performed. Lungs were excised, and tissue sections evaluated for inflammatory cell influx, α-smooth muscle actin, collagen, biglycan, and Dcn deposition. Changes in TH-2 cytokine mRNA and protein were also measured. Airway resistance was increased in OA-challenged Dcn(+/+) mice only (P < 0.05), whereas tissue elastance and damping were increased in both OA-challenged Dcn(+/+) and Dcn(-/-), but more so in Dcn(+/+) mice (P < 0.001). Inflammation and collagen staining within the airway wall were increased with OA in Dcn(+/+) only (P < 0.001 and P < 0.01, respectively, vs. saline). IL-5 and IL-13 mRNA were increased in lung tissue of OA-challenged Dcn(+/+) mice. Dcn deficiency resulted in more modest OA-induced hyperresponsiveness, evident at the level of the central airways and distal lung. Differences in physiology were accompanied by differences in inflammation and remodeling. These findings may be, in part, due to the well-described ability of Dcn to bind transforming growth factor-β and render it less bioavailable.
Objective This project aims to prospectively and objectively assess otolaryngological manifestations and quality of life of children with primary ciliary dyskinesia (PCD) and compare these findings with healthy pediatric controls. Study Design Cross-sectional. Setting Two high-volume pediatric PCD specialty centers. Methods Standardized clinical assessment; Sino-Nasal Outcome Test 22 (SNOT-22); Hearing Environment and Reflection Quality of Life (HEAR-QL); Reflux Symptom Index (RSI); standardized physical examination of the sinonasal, laryngeal, and otological systems; and investigations including pure-tone audiograms (PTAs) and sinonasal cultures were collected. Results Forty-seven children with PCD and 25 control participants were recruited. Children with PCD had more upper airway symptoms than healthy children. They had significantly higher scores in both SNOT-22 and RSI, indicating worse sinonasal and reflux symptoms, with worse quality of life on the HEAR-QL index compared to healthy children ( P < .05). Fifty-two percent of children with PCD-related hearing loss were not aware of their hearing deficit that was present on audiological assessment, and only 23% of children who had ventilation tubes had chronic otorrhea, most of which was easily controlled with ototopic drops. Furthermore, although all children with PCD had chronic rhinosinusitis, only 36% of them were using topical nasal treatment. The most common bacteria cultured from the middle meatus were Staphylococcus aureus in 11 of 47 (23%), followed by Streptococcus pneumoniae in 10 of 47 (21%). Conclusion This multisite cohort highlights the importance of otolaryngology involvement in the management of children with PCD. More rigorous otolaryngological management may lead to reductions in overall morbidity and improve quality of life for children with PCD.
Background: Mechanical ventilation (MV) is associated with changes in autonomic nervous system activity in preterm infants, which can be assessed by measurements of heart rate variability (HRV). Decreased HRV has been described in adults undergoing disconnection from MV; such information is not available in preterm infants. Objective: To compare differences in HRV between infants successfully extubated and those who failed, and to evaluate the accuracy of HRV as a predictor of extubation readiness. Methods: This is a prospective, observational study of infants with a birth weight ≤1,250 g undergoing their first extubation attempt. Heart rate was measured during a 60-min period immediately prior to extubation and HRV was calculated using the frequency domain analysis. Results: A total of 47 infants were studied; 36 were successfully extubated and 11 reintubated. There were no differences in patient demographics, ventilator settings, blood gases or postextubation management between the groups. All components of the HRV analysis were significantly decreased in infants who failed, generating high areas under the receiver operating characteristic curve. The specificity and positive predictive values were 100, but with limited sensitivity and negative predictive values. Conclusions: Infants considered ‘ready to be extubated' but who subsequently failed their first extubation attempt had decreased HRV prior to extubation. Though promising, the value of HRV as a predictor of extubation readiness requires further evaluation.
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