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

Abstract

Background and AimIn 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.MethodsSerial 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.ResultsPaO2 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.ConclusionIn 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.

Clinical and Pulmonary Function Markers of Respiratory Exacerbation Risk in Subjects With Quadriplegic Cerebral Palsy

“…In our study group, P aO 2 (mean of 81.07 Ϯ 23.50 mm Hg) approximated the lowest limit defining normal oxygenation in children, that is 80 mm Hg. 24 In this context, higher P aCO 2 in patients with high exacerbation risk may be linked to an attenuated ventilatory response to the metabolic demand of O 2 consumption. Taking this hypothesis a step further, we speculate that diminished ventilatory response may predispose patients to development of clinically relevant exacerbations due to a failure to compensate for an increased ventilatory demand.…”

“…Sampling of arterialized capillary blood was preferred to arterial puncture or catheterization because it is technically simpler and less likely to result in serious complications; research has shown that this method provides sufficiently accurate measurements of P aO 2 and P aCO 2 . 24 Airway resistance was measured by the interrupter technique; this simple test, which requires only passive cooperation, provides an accurate estimate of airway resistance. 25 Home overnight S pO 2 monitoring was performed within 3 nights of entering the study.…”

Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis

“…Measurement techniques have been described in detail previously. [8][9][10]37 All values were expressed by z-transformation in SD scores (SDS), based on gender-and age-specific regression equations. 38,39 Details regarding measurement techniques and clinical evidence of these target parameters are given in the online data supplement.…”

“…3 Clinically, CF is characterized by elevated sweat chloride concentration, exocrine pancreatic insufficiency, male infertility and progressive obstructive lung disease, the latter being the primary cause of mortality. 4,5 The respiratory disease progression in CF is expressed by various pulmonary dysfunctions, [6][7][8][9][10] such as ventilation inhomogeneities, 8,11 pulmonary hyperinflation, 9,12 bronchial obstruction, trapped gas and gas exchange disturbances, 10 most of them occurring early in life, 7,12,13 and progressing even in the absence of clinical signs and symptoms. 11,14,15 Owing to the great phenotypic variability in lung disease even observed among patients carrying the same CFTR genotype, several association studies have been conducted to find modifying genetic factors and to study their influence on CF disease outcome.…”

“…To achieve this, we used the clinically very carefully characterized patient cohort of the Children's University Hospital in Bern documented over a time period of 13 years. [8][9][10] Owing to the fact that these patients were treated at the same hospital, environmental influences in the context of medical treatment are reduced in this cohort, making it well suited to study-modifying effects.…”