Distinct type I collagen alterations cause intrinsic lung and respiratory defects of variable severity in mouse models of osteogenesis imperfecta.

Type I collagen alterations cause osteogenesis imperfecta (OI), a connective tissue disorder characterized by severe bone fragility. Patients with OI can suffer from significant pulmonary manifestations including severe respiratory distress in the neonatal period and a progressive decline in respiratory function in adulthood. We and others have shown intrinsic lung defects in some mouse models of OI. In this large study, we performed histological, histomorphometric, microcomputed tomography and invasive studies on oim/+, Col1a2+/G610C , CrtapKO and oim/oim mice, mimicking mild to moderate to severe OI, with the overall goal of determining the extent of their pulmonary and respiratory mechanics defects and whether these defects correlate with the skeletal disease severity and affect each sex equally. Although with variable severity, OI lung histology consistently showed alveolar simplification with enlarged acinar airspace and reduced alveolar surface. Numerous respiratory mechanics parameters, including respiratory system resistance and elastance, tissue damping, inspiratory capacity, total lung capacity, and others, were significantly and similarly impacted in CrtapKO and oim/oim but not in oim/+ or Col1a2+/G610C compared to control mice. Our data indicate that the impact of type I collagen alterations and OI on lung morphology and function positively correlate with the severity of the extracellular matrix deficiency. Moreover, the respiratory defects were more pronounced in male compared to female mice. It will be important to determine whether our observations in mice translate to OI patients and to dissect the respective contribution of intrinsic lung defects vs. extrinsic skeletal defects to impaired lung function in OI. KEY POINTS: Different type I collagen alterations in mouse models of osteogenesis imperfecta (OI) cause similar abnormal lung histology, with alveolar simplification and reduced alveolar surface, reminiscent of emphysema. Several respiratory mechanics parameters are altered in mouse models of OI. The impact of type I collagen alterations and OI on lung morphology and function positively correlate with the severity of the extracellular matrix deficiency. Respiratory defects were more pronounced in male compared to female mice. It will be important to determine whether our observations in mice translate to OI patients and to dissect the respective contribution of intrinsic lung defects vs. extrinsic skeletal defects to impaired lung function in OI.

Haploinsufficiency of Col5a1 causes intrinsic lung and respiratory changes in a mouse model of classical Ehlers-Danlos syndrome.

The Ehlers-Danlos syndromes (EDS) are inherited connective tissue diseases with primary manifestations that affect the skin and the musculoskeletal system. However, the effects of EDS on the respiratory system are not well understood and are described in the literature as sporadic case reports. We performed histological, histomorphometric, and the first in-depth characterization of respiratory system function in a mouse model of classical EDS (cEDS) with haploinsufficiency of type V collagen (Col5a1+/-). In young adult male and female mice, lung histology showed reduced alveolar density, reminiscent of emphysematous-like changes. Respiratory mechanics showed a consistent increase in respiratory system compliance accompanied by increased lung volumes in Col5a1+/- compared to control mice. Flow-volume curves, generated to mimic human spirometry measurements, demonstrated larger volumes throughout the expiratory limb of the flow volume curves in Col5a1+/- compared to controls. Some parameters showed a sexual dimorphism with significant changes in male but not female mice. Our study identified a clear respiratory phenotype in the Col5a1+/- mouse model of EDS and indicated that intrinsic respiratory and lung changes may exist in cEDS patients. Their potential impact on the respiratory function during lung infections, other respiratory disease processes, or insults may be significant and justify further clinical evaluation.

A term neonate with cyanosis with crying.

Congenital short trachea can be associated with bronchial compression with associated symptoms of apnoea, cyanosis, increased work of breathing, and/or respiratory failure in infancy. Operative intervention should be considered in symptomatic cases. https://bit.ly/3gM6Vv9.

Comparative Effectiveness of Intranasal Dexmedetomidine-Midazolam versus Oral Chloral Hydrate Targeting Moderate Sedation during Pediatric Transthoracic Echocardiograms.

Objective To compare efficacy and safety of two moderate sedation regimens for transthoracic echocardiography (TTE): intranasal dexmedetomidine-midazolam (DM) versus oral chloral hydrate (CH) syrup. Method This was a retrospective cohort of 93 children under 4 years of age receiving moderate sedation with either DM or CH for TTE from January 2011 through December 2014. Measurements and Main Results Forty-nine patients received oral CH and 44 received the intranasal combination of DM. The demographics between groups were similar except the DM patients were slightly older and heavier (each p < 0.05). Failure rate between groups did not reach statistical significance (CH 14.3% vs. DM 6.8%; p = 0.324). Total sedation to discharge time was similar between groups (CH 89.4 minutes vs. DM 89.6 minute; p = 0.97). Cardiopulmonary data did reveal a significantly lower heart rate (101.9 vs. 91.7; p < 0.001) and respiratory rate (23.4 vs. 21.0, p = 0.03) in the DM group, but no difference in blood pressure measurements or echo determined shortening fraction. Conclusion These data support the use of intranasal DM as a safe and efficacious method of moderate sedation for children undergoing TTE.