Dataset Information

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis.

ABSTRACT:

Background and aim

In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.

Methods

Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination.

Results

PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes.

Conclusion

In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation.

SUBMITTER: Kraemer R

PROVIDER: S-EPMC2780404 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Publications

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis.

Kraemer Richard R Latzin Philipp P Pramana Isabelle I Ballinari Pietro P Gallati Sabina S Frey Urs U

Respiratory research 20091112

<h4>Background and aim</h4>In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.<h4>Methods</h4>Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, provid ...[more]

PMID: 19909502

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Project description:Background: HIV infection is associated with impaired gas transfer in the lung as indicated by a low diffusing capacity (DLCO). Mechanisms for reduced DLCO in the setting of HIV infection are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood gene expression. Methods: A total of 40 HIV-infected (HIV+) and uninfected (HIV-) men with preserved versus reduced DLCO were selected from a larger cohort study of lung function. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from peripheral blood leukocytes (PBLs) and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV+ vs. HIV- subjects with preserved DLCO and those with impaired DLCO to identify differentially activated pathways. Results: Using pathway-based analyses we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. When we applied a similar analysis to subjects with low DLCO, we identified a much broader repertoire of inflammatory and immune-related pathways in HIV+ patients relative to HIV- subjects, with up-regulation of multiple interleukin pathways, interferon signaling, Toll-like receptor signaling, and T cell/B cell receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV+ patients with reduced DLCO relative to the other groups. Conclusions: Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated pulmonary gas exchange impairment. Total RNA was isolated from peripheral blood leukocytes in four subject groups: 1. HIV-, low DLCO (N = 11); 2. HIV+, low DLCO (N = 10); 3. HIV-, preserved DLCO (N = 9); 4. HIV+, preserved DLCO (N = 9). Each sample was hybridized to an Affymetrix PrimeView Human Gene Expression microarray for a total of 39 experiments.

Dataset Information

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis.

Background and aim

Methods

Results

Conclusion

Publications

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis.

Similar Datasets

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