American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2019
ReviewClinical, Histopathological, and Molecular Diagnostics in Lethal Lung Developmental Disorders.
Lethal lung developmental disorders are a rare but important group of pediatric diffuse lung diseases presenting with neonatal respiratory failure. On the basis of histopathological appearance at lung biopsy or autopsy, they have been termed: alveolar capillary dysplasia with misalignment of the pulmonary veins, acinar dysplasia, congenital alveolar dysplasia, and other unspecified primary pulmonary hypoplasias. However, the histopathological continuum in these lethal developmental disorders has made accurate diagnosis challenging, which has implications for recurrence risk. ⋯ Application of next-generation sequencing techniques, including exome sequencing and whole-genome sequencing, has demonstrated their complex compound inheritance. These data indicate that noncoding regulatory elements play a critical role in lung development in humans. We propose that for more precise lethal lung developmental disorder diagnosis, a diagnostic pathway including whole-genome sequencing should be implemented.
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Am. J. Respir. Crit. Care Med. · Nov 2019
Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors.
Rationale: Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. However, possibly adverse effects of e-cig vapor in never-smokers are not well understood. Objectives: To test the effects of nicotine-containing e-cig vapors on airway mucociliary function in differentiated human bronchial epithelial cells isolated from never-smokers and in the airways of a novel, ovine large animal model. ⋯ Importantly, nebulized A967079 reversed the effects of e-cig liquid on sheep tracheal mucus velocity. Conclusions: Our findings show that inhalation of e-cig vapor causes airway mucociliary dysfunction in vitro and in vivo. Furthermore, they suggest that the main nicotine effect on mucociliary function is mediated by TRPA1 and not nicotinic acetylcholine receptors.
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Am. J. Respir. Crit. Care Med. · Nov 2019
The Projected Economic and Health Burden of Uncontrolled Asthma in the United States.
Rationale: Despite effective treatments, a large proportion of patients with asthma do not achieve sustained asthma control. The "preventable" burden associated with lack of proper control is likely taking a high toll at the personal and population level. Objectives: We predicted the future excess health and economic burden associated with uncontrolled asthma among American adolescents and adults for the next 20 years. ⋯ Across states, the average 20-year per capita costs due to uncontrolled asthma ranged from $2,209 (Arkansas) to $6,132 (Connecticut). Conclusions: The burden of uncontrolled asthma is substantial and will continue to grow. Given that a substantial fraction of this burden is preventable, better adherence to evidence-informed asthma management strategies by care providers and patients has the potential to substantially reduce costs and improve quality of life.