Alexandra Hebestreit

Assessment of human pulmonary function using oxygen-enhanced T1 imaging in patients with cystic fibrosis

Indirect qualitative MRI of pulmonary function is feasible using the paramagnetic effects of oxygen physically dissolved in blood. In this study, a more quantitative oxygen‐enhanced pulmonary function test based on the slope of a plot of R1 vs. oxygen concentration—the oxygen transfer function (OTF)—was developed and tested in a pool of five healthy volunteers and five patients with cystic fibrosis (CF). The lung T1 relaxation rate, R1, under normoxic conditions (room air, 21% O2), and the response to various hyperoxic conditions (40%–100% O2) were studied. Lung T1 in healthy volunteers showed a relatively homogeneous distribution while they breathed room air, and a homogeneous decrease under hyperoxic conditions. Lung T1 in CF patients showed an inhomogeneous distribution while they breathed room air, and the observed lung T1 decrease under hyperoxia depended on the actual state of the diseased lung tissue. In the selected group of CF patients, areas with reduced OTF also showed reduced perfusion, as confirmed by qualitative contrast‐enhanced MR pulmonary perfusion imaging. The results demonstrate that this completely noninvasive oxygen‐enhanced pulmonary function test has potential for clinical applications in the serial diagnosis of lung diseases such as CF. Magn Reson Med 51:1009–1016, 2004.

Ventilatory threshold: a useful method to determine aerobic fitness in children?

PURPOSE The objective of this study was to assess intra- and inter-evaluator reliability and validity of ventilatory threshold (VT) determination in children. METHODS At the age of 6-12 yr, 35 children born prematurely and 20 controls born at term performed an incremental continuous cycling task until volitional fatigue. Fifteen-second averages of VE/VO2, VE/VCO2, and respiratory exchange ratio were plotted 1) over time (X-time) and 2) over VO2 (X-VO2). VCO2 was plotted over VO2 only (X-VO2). Two experienced evaluators, blind to the identity of plots, independently assessed VT from X-time and X-VO2 plots on two occasions, 6 wk apart. Thus, for each of the 55 subjects, four VT values were expected from X-time plots and four from X-VO2 plots (2 evaluators, 2 occasions). RESULTS VT expressed as VO2 in mL x min(-1) could be determined by both evaluators on both occasions in 40/55 children from X-time and in 45/55 children from X-VO2. VT was significantly different between evaluators for X-time plots. Using X-time plots, intraevaluator ICC were 0.88 and 0.98 and interevaluator ICC were 0.82 and 0.79. The respective values for X-VO2 plots were 0.94 and 0.95, and 0.96 and 0.92. Intra- and inter-evaluator reliability of VT determinations tended to be slightly lower in children born prematurely compared with those born at term. There was a close association between VT and VO2peak (r = 0.92). CONCLUSION Plotting gas exchange data over VO2 is likely to be the method of choice for determining VT. Although a minority of children have uninterpretable X-VO, plots, VT can be reliably interpreted in the remainder. Furthermore, VT is a valid marker of aerobic capacity. Thus, VT is a useful measure of aerobic fitness in children.

Persistence of Candida species in the respiratory tract of cystic fibrosis patients

It is still controversial as to whether Candida spp. are transient or persistent colonizers of the respiratory tract of cystic fibrosis (CF) patients. We conducted a prospective study of 56 CF patients over a 30 month period to assess the distribution and persistence of different Candida spp. In vitro antifungal susceptibility testing was performed and the C. albicans isolates were typed with CARE-2 hybridization and other Candida spp. by RAPD-PCR for persistence and transmission. We found that the mean persistence of the most frequent Candida spp. was >or= 9 months. In patients from whom more than 10 isolates were recovered, we noted that at least 30% were genetically related and transmission of C. albicans in siblings was observed. The majority of all isolates were susceptible to all antifungals tested. We concluded that there was long-term persistence of Candida in the respiratory tract of CF patients and that transmission between siblings may be one possible means of acquisition. Whether long-term colonization with Candida strains can contribute to the chronic infection and inflammation in the CF lung requires further investigation.

Molecular typing and colonization patterns of Aspergillus fumigatus in patients with cystic fibrosis

Aspergillus fumigatus is a chronic colonizer of the respiratory tract of patients with cystic fibrosis (CF). A total of 204 A. fumigatus isolates from 36 CF patients from three different medical centers, collected over a period of four months till 9.5 years, were genotyped using the short tandem repeat panel for A. fumigatus (STRAf assay). Four different colonization patterns were observed. Colonization patterns with only unique genotypes were found in 36% of the patients. In contrast 17% of the patients were chronically colonized with a single genotype. The remaining patients showed a predominant genotype or genotypes that succeed each other. In this collection no relation was found between colonization patterns and allergic bronchopulmonary aspergillosis.

Effect of supervised training on FEV1 in cystic fibrosis: A randomised controlled trial

BACKGROUND Long-term exercise interventions have been shown to improve vital capacity in cystic fibrosis (CF). Yet, no data are available indicating positive effects of long-term exercise training on FEV1. METHODS 39 Swiss patients with CF were randomly divided into strength training (ST, n=12), endurance training (AT, n=17) and controls (CON(CH), n=10), and also compared with age-matched Swiss (n=35) and German (n=701) CF registry data. A partially supervised training of 3×30 min/week for 6 months took place with measurements at baseline and after 3, 6, 12 and 24 months. Primary outcome was FEV1 at 6 months. RESULTS FEV1 increased significantly in both training groups compared with CON(CH) (AT:+5.8±0.95, ST:+7.4±2.5, CON(CH):-11.5±2.7% predicted, p<0.001) and both registry groups at 6 months. At 24 months, changes in favour of the training groups persisted marginally compared with CONCH, but not compared with registry data. CONCLUSIONS A partially supervised training over 6 months improved FEV1 but effects were basically gone 18 months off training. Regular long-term training should be promoted as essential part of treatment in CF.

Quantitative perfusion mapping of the human lung using 1H spin labeling

To evaluate the feasibility and reproducibility of a noninvasive, rapid and quantitative pulmonary perfusion mapping method using a two‐compartment tissue model in combination with a 1H spin labeling technique.

Risks associated with exercise testing and sports participation in cystic fibrosis.

BACKGROUND Severe adverse reactions (SARs) associated with physical exercise have not been systematically studied in cystic fibrosis (CF). METHODS Two surveys were conducted to assess the incidence of exercise-related SARs: a caregiver survey asking for complications associated with exercise testing and in-hospital training therapy and a web-based patient survey asking for problems with exercise. RESULTS 78 of 107 CF facilities caring for 4208 patients responded to the caregiver survey, 256 patients answered the web-based survey. No SARs were reported for 713 exercise tests. With in-hospital training, the yearly incidence of exercise-related SARs such as pneumothorax, cardiac arrhythmia, injury or hypoglycaemia was <1% each, the respective lifetime incidences reported by the patients were 0.8-6.3%. 67% of the patients reported no SARs with exercise. CONCLUSIONS Exercise testing is safe in patients with CF. Despite the limitations in quality of data, the incidence of exercise-related SARs appears low in this population.

Magnetization transfer short inversion time inversion recovery enhanced 1H MRI of the human lung

The unique characteristics of the human lung arising from low proton density and multiple air-tissue interfaces of the alveoli cause difficulty in1H lung magnetic resonance imaging. In addition, the dominating signal from sources such as the thoracic muscle and subcutaneous fat hampers the visualization of the lung parenchyma. In this contribution, an efficient tissue suppression technique is presented which allows one to significantly enhance lung parenchyma visibility. A short inversion time inversion recovery (STIR) experiment combined with a magnetization transfer (MT) experiment was used for magnetization preparation in order to suppress the signal from muscle. A half-Fourier single-shot turbo spin-echo sequence was used as acquisition module. This approach was used to perform lung anatomical imaging in eight healthy human subjects and five patients withcystic fibrosis. The results obtained demonstrate that with MT-STIR approach high quality human lung images can be obtained and that this approach has the potential for the evaluation of lung pathologies.