For that purpose mean values of lung function data were computed for the age range of 5 to 8 years for each patient. Using a two-test analysis by z-score, comparisons of PaO 2 with chi-square statistics cross tabulation demonstrated that the best association was found for FRC pleth Chi -square: V TG was not significantly associated.
The association between oxygenation and pulmonary hyperinflation is presented in Figure 3 panel A. In A further As FEV 1 is still considered to be one of the best predictors of progression in CF, we investigated whether a differentiation between normoxemia and hypoxemia can be correlated with this spirometric function parameter. Figure 3 , panel B demonstrates that It is noteworthy that these patients already had a significant deficit in oxygenation as shown by the PaO 2 , while FEV 1 remained within normal limits,.
Crosstab comparison of initial z -scores mean during age range of 5 to 8 years between A , PaO 2 and FRC pleth presenting pulmonary hyperinflation in association with hypoxemia and B PaO 2 and FEV 1 , to present the portion of normal FEV 1 measurements while already hypoxemic, obtained in CF patients.
In Figure 4 stratification of measurements was performed for normocarbia versus hypocarbia, divided into those with normal versus abnormal FEV 1 in relation to oxygenation. The question arose whether or not patients presenting with hypocarbia have an advantage with respect to oxygenation.
The present observational study illustrates the complexity of gas exchange in children with cystic fibrosis, especially with reference to the age-related changes in oxygenation. The age-related deterioration of oxygenation has not yet been well described, presumably due to the fact that gas exchange characteristics are not routinely evaluated over a period of a substantial number of years.
Our study, performed in a representative number of cases and followed-up over a consistent number of years demonstrates that oxygenation is specifically influenced by different lung function deficits and CF genotypes.
There are several major findings of this study: First, i a linear decline in oxygenation could be demonstrated over the age range 5 to 18 years, which was closely and independently related to the degree of pulmonary hyperinflation FRC pleth , the degree of flow and volume limitation FEV 1 , FEF 50 , and ventilation inhomogeneities LCI.
Secondly, ii as reported for several lung function parameters [ 1 , 2 ], the decline in PaO 2 is representative of an overall deterioration of lung disease, reflecting that factors such as the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function are involved in the long-term course of gas exchange characteristics. Most importantly, however, iii in more than half the patients with hypoxemia, FEV 1 was within the range of normal values, and hence with functional deficits not detectable by spirometric lung function testing alone.
Furthermore, iv an association could be found between oxygenation and the genotype. It follows that PaO 2 may serve as a sensitive marker of lung function deterioration in CF. The present study demonstrates that the preservation of airway function and hence an intact static recoil of the lungs over years is essential, as has been shown by Zapletal [ 44 ].
It was reported by Hart et al. Pulmonary hyperinflation and ventilation inhomogeneities are further pathophysiologic characteristics, which have to be taken into consideration regarding progression in CF, as reported previously by our group [ 1 , 2 ]. A detailed discussion about blood gas measurements in children, the stratification into genetic subgroups, limitations in the interpretation of extensive lung function tests and the different options for statistical modeling are given in the additional file 1.
An important limitation of this type of data resides in the ability to obtain repeated measurements of lung function annually over a substantial period of time. Although the technique of blood gas measurements from the arterialized earlobe is well established and routinely used in several laboratories [ 26 , 27 , 32 — 34 ], in the following some technical aspects have to be mentioned. Finally, limitation of collected functional data over a wide range of years may include confounders related to changes in the technical set-up.
As proposed by Soni et al [ 16 ], we assessed the influence of these potential confounders by 3 characteristics such as "year at birth", "year at diagnosis" and the "year at testing".
The "year at test" proved to be the principal confounder influencing the course of PaO 2. Most important finally, the variances of lung function over age are specific for each lung function parameter. Therefore, values of lung function data have to be expressed by z-scores, calculated from age- and gender-specific equations for value prediction for each lung function parameter, and in particular also for each lung function device as previously presented [ 1 , 2 ].
Currently direct arterial catheterization of the radial artery is the widely accepted gold standard technique for obtaining the most accurate assessment of pulmonary gas exchange, especially in adult medicine.
However, this technique is painful and not suitable for use in children for long-term evaluation. Alternative non-invasive methods have been proposed such as pulse oxymetry, which is used to assess arterial oxyhemoglobin saturation. However, obtained values correlated poorly with arterial PaO 2 values [ 33 ]. Pulse oxymetry is a poor predictor of PaO 2 because of the sigmoidal shape of the oxyhemoglobin dissociation curve and because the curve can be shifted under various clinical and physiological conditions.
Therefore, capillary arterialized blood gas analysis is a very convenient technique especially suitable for children and for repeated measurements. Comparisons between earlobe capillary PaO 2 and radial arterial PaO 2 were performed by Godfrey et al.
The former author group compared earlobe and arterial values in 8 adult subjects age range of 26 to 63 years at rest and on exercise, showing that the mean difference between arterial and earlobe samples for PaO 2 at rest was 2. It was concluded that sampling blood from the earlobe is appropriate as a substitute for arterial PaO 2 , provided certain important methodological conditions such as sampling site and optimal vasodilatation are fulfilled. In a study examining PaO 2 measurements over a long period of time, it would be preferable to validate the results periodically using arterial samples.
It is, however, difficult to justify arterial blood sampling in a collective of CF children with no or only minor pulmonary function impairments. In a meta-analysis performed by Zavorsky et al. However, the discrepancy between capillary and arterial PaO 2 increased with increasing PaO 2.
Reproducibility of earlobe blood gas measurements was assessed by Godfrey et al. Moreover, hypocarbia in CF is poorly described in the literature and the correlation of gas exchange characteristics with lung function is unknown. There is only one report in which the association between hypocarbia and hypercapnia and the matching of ventilation has been studied in dogs [ 45 ]. The present report focuses on the decline of oxygenation in CF. As demonstrated in Table 2 , oxygenation is significantly associated with the degree of flow limitation given by the FEV 1.
This finding is in line with Hirsch et al. Ventilation appears mechanically inefficient but necessary to keep arterial PaCO 2 from rising and oxygen saturation from falling at rest [ 46 ]. Moreover, Hart et al. Other physiologic studies have demonstrated an increase in tidal volume V T with a reduction in respiratory rate RR in association with impairment of gas exchange [ 28 ].
The present study indicates that oxygenation at rest is significantly associated with LCI and with FRC pleth and reduced forced expiratory volume FEV 1 as an indirect parameter of airflow limitation. To date, a relationship between CFTR genotypes and severity of pulmonary disease has proven difficult to determine [ 47 ]. The present study, however, clearly demonstrates an association between gas exchange characteristics especially oxygenation and genotypes. These findings are in line with previous work obtained in infants [ 13 ] and children [ 1 , 2 ] with CF.
Schaedel et al. Since these patients generally had a sufficient level of pancreatic function, it was concluded that CFTR genotypes associated with long-term pancreatic sufficiency have more benign lung disease and better pulmonary function [ 12 , 14 ]. With the exception of one patient with a missense mutation, all patients in our study collective presented with pancreatic insufficiency, requiring continuous supplementation with pancreatic enzymes and high caloric nutritional support.
The major new finding in the present study is an allocation of specific genotypes to i sufficient oxygenation combined with low PaCO 2 levels, and ii insufficient oxygenation combined with normocarbia, reflecting different phenotypes of disease progression.
However, further experiments are needed to elucidate the fate of the insT protein in the cell after its biosynthesis. In conclusion , the linear decline of PaO 2 over the years was closely associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities, and parameters of airway function on the one hand and with genotypes on the other hand. Since the assessment of factors influencing the overall estimate of gas exchange is of major interest to understand functional deficits influencing progression not only in quantitative, but also in qualitative terms, classification into certain functional risk groups may have implications for therapeutical intervention.
However, further studies are needed to demonstrate whether changes in PaCO 2 in relation to PaO 2 are potential predictors of exacerbation or of the long-term clinical outcome. We keep in mind, that the ability of blood gas measurements to serve as outcome measures in interventional studies largely depends from the knowledge to what extent changes recorded during a short-term study will be out of the variability of the measurement changes established by the present long term approach over years.
Article PubMed Google Scholar. Respir Res , 7: Gustafsson PM, Aurora P, Lindblad A: Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis.
Eur Respir J , — Pediatr Pulmonol , — Beardsmore CS: Lung function from infancy to school age in cystic fibrosis. Arch Dis Child , — Kraemer R, Schoni MH: Ventilatory inequalities, pulmonary function and blood oxygenation in advanced states of cystic fibrosis. Respiration , — Thorax , — Lancet , — J Pediatr , — Pediatr Res , — In Perspectives in Cystic Fibrosis. Edited by: Sturgess JM. Mississanga, Ontario: Imperial Press; Google Scholar. J Cyst Fibros , 7: — J Chronic Dis , — Cystic Fibrosis Foundation Consensus Panel.
Eur J Hum Genet , 7: — Bennett LC, Kraemer R, Liechti-Gallati S: Buccal cell DNA analysis in premature and term neonates: screening for mutations of the complete coding region for the cystic fibrosis transmembrane conductance regulator.
Eur J Pediatr , 99— Some of these lung diseases start with a persistent inflammatory reaction which takes place in the air sacs alveoli. In other forms, it is not so much the inflammatory reaction that is the prominent feature but, as we now believe, more the damage to the lining cells epithelium of the alveoli. Both processes subsequently result in increased formation of connective tissue and thus in fibrosis.
This scar tissue forms both in the alveoli and between them, and in some forms around the airways bronchi.
Eventually there is also extensive loss of normally formed alveoli. The results from this test can show how severe your disease is and if you need oxygen therapy The goals of treatment for respiratory insufficiency include: Relieving your symptoms Slowing the progress of the disease Improving your exercise tolerance your ability to stay active Preventing and treating complications Improving your overall health Various treatments are used to treat respiratory insufficiency, including:.
Treatment Description Pulmonary rehabilitation Pulmonary rehabilitation is a program of exercise, education, and support to help you learn to breathe—and function—at the highest level possible. Rehabilitation activities can make a substantial difference in slowing the progression of lung conditions and helping you stay active.
Oxygen therapy When the oxygen level in your blood becomes low, oxygen therapy may be prescribed. Usually a nasal cannula connected to an oxygen source is worn beneath the nose. At home, this oxygen source may be an oxygen cylinder or an oxygen concentrator. In hospitals, there are oxygen sources readily available.
Ventilation A mechanical ventilator is a device that makes it easier for you to breathe by providing your lungs with pressurized volumes of air.
Medications Medications may relax the muscles around your airways, helping them open wider. These medications may include bronchodilators and inhaled glucocorticosteroids steroids.
Surgery Surgery usually is a last resort for people who have severe symptoms that have not improved with other treatments. Types of surgeries include bullectomy and lung volume reduction surgery.
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