American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2012
Neurogenic changes in the upper airway of patients with obstructive sleep apnea.
Controversy persists regarding the presence and importance of hypoglossal nerve dysfunction in obstructive sleep apnea (OSA). ⋯ These results confirm and quantify the extent and existence of structural neural remodeling in OSA.
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Am. J. Respir. Crit. Care Med. · Feb 2012
Increased nicotinamide adenine dinucleotide phosphate oxidase 4 expression mediates intrinsic airway smooth muscle hypercontractility in asthma.
Asthma is characterized by disordered airway physiology as a consequence of increased airway smooth muscle contractility. The underlying cause of this hypercontractility is poorly understood. ⋯ Our findings support a critical role for NOX4 overexpression in asthma in the promotion of oxidative stress and consequent airway smooth muscle hypercontractility. This implicates NOX4 as a potential novel target for asthma therapy.
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α(1)-Antitrypsin (AAT) deficiency is an underrecognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase). Among the approximately 120 variant alleles described to date, the Z allele is most commonly responsible for severe deficiency and disease. ⋯ In addition to the usual treatments for emphysema, infusion of purified AAT from pooled human plasma-so-called "augmentation therapy"-represents a specific therapy for AAT deficiency and raises serum levels above the protective threshold. Although definitive evidence from randomized controlled trials of augmentation therapy is lacking and therapy is expensive, the available evidence suggests that this approach is safe and can slow the decline of lung function and emphysema progression. Promising novel therapies are under active investigation.
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Am. J. Respir. Crit. Care Med. · Feb 2012
Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.
Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood. ⋯ Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.