American journal of respiratory cell and molecular biology
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Am. J. Respir. Cell Mol. Biol. · Sep 2003
Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease.
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) genotype does not explain the heterogeneity observed in CF pulmonary disease severity. Modifier genes are implicated for this heterogeneity. alpha1-antitrypsin (alpha1-AT) is one of the few antiproteases capable of inactivating neutrophil elastase. We investigated whether alpha1-AT alleles (Z, S deficiency alleles and the 3' G1237-->A mutation) were associated with increased disease severity and the alpha1-AT acute phase response during pulmonary exacerbations. ⋯ There were 69, 13, and 18 patients with CF who were MS, SS, and MZ, respectively. There were 95 and 7 patients with CF heterozygous or homozygous for the A1237 allele, respectively. alpha1-AT genotype did not predict pulmonary disease severity, and was not associated with more severe clinical outcome (death or lung transplantation) or age of onset of Pseudomonas aeruginosa infection. Body mass index was a significant predictor of alpha1-AT levels during exacerbations. alpha1-AT genotype is not a major contributor to the variability of pulmonary disease severity in CF.
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Am. J. Respir. Cell Mol. Biol. · Sep 2003
Airway obstruction in sheep with burn and smoke inhalation injuries.
The goals of this study were (i) to compare the degree and (ii) temporal changes in airway obstruction in sheep with pulmonary injury induced by smoke inhalation and/or burn; (iii) to qualitatively assess the cellular and mucous content of obstructive material; and (iv) to statistically assess a possible relationship between the degree of airway obstruction and pulmonary dysfunction. Using masked histologic slides, we estimated the degree of luminal obstruction in all cross-sectioned airways. The mean degree of bronchial, bronchiolar, and terminal bronchiolar obstruction was significantly greater in animals with smoke injury alone or combined smoke inhalation and burn (S+B) injury, compared with animals with burn injury alone or uninjured animals (P < 0.05). ⋯ Localization of specific mucin subtypes in S+B tissues suggests that increasing bronchiolar obstruction is derived, in part, from upper airway material. Multiple linear regression analysis of airway obstruction scores compared with PaO2/FIO2 values showed a correlation coefficient of r = 0.76, with bronchial and bronchiolar scores predictive of PaO2/FIO2, (P < 0.05). These results suggest that strategies to remove or decrease formation of upper airway obstructive material may reduce its deposition into small airways and parenchyma and may improve respiratory function in victims of smoke inhalation injury.