Elexacaftor/tezacaftor/ivacaftor improves nasal nitric oxide in patients with cystic fibrosis.

BACKGROUND: In health, nitric oxide (NO) shows high concentrations in the upper airways, while nasal NO (nNO) is significantly lower in patients with sinonasal inflammation, such as people with cystic fibrosis (PwCF). In PwCF treated with elexacaftor/tezacaftor/ivacaftor (ETI; PwCF-ETI), clinical improvement of sinonasal symptoms and inflammation was observed. We therefore hypothesised that ETI may increase nNO in PwCF. METHODS: 25 PwCF-ETI underwent nNO measurement at baseline and after 3 to 24 months of ETI treatment. NNO was measured using velum closure (VC) techniques in cooperative patients and tidal breathing (TB) for all patients. As controls, 7 CF patients not eligible for ETI (PwCF-non ETI) and 32 healthy controls (HC) were also repeatedly investigated. RESULTS: In PwCF-ETI, sinonasal symptoms, lung function parameters and sweat chloride levels improved from baseline to follow-up whereas there was no change in PwCF-non ETI and HC. NNO increased from a median (IQR) value at baseline to follow-up from 348.2 (274.4) ppb to 779.6 (364.7) ppb for VC (P < 0.001) and from 198.2 (107.0) ppb to 408.3 (236.1) ppb for TB (P < 0.001). At follow-up, PwCF-ETI reached nNO values in the normal range. In PwCF-non ETI as well as HC, nNO did not change between baseline and follow-up. CONCLUSIONS: In PwCF-ETI, the nNO values significantly increased after several months of ETI treatment in comparison to baseline and reached values in the normal range. This suggests that nNO is a potential non-invasive biomarker to examine sinonasal inflammatory disease in PwCF and supports the observation of clinical improvement in these patients.

Multiple-breath washout to detect lung disease in patients with inborn errors of immunity.

Background: Pulmonary manifestations are the major cause of morbidity and mortality in patients with inborn errors of immunity (IEI). New and more sensitive diagnostic methods can potentially lead to earlier recognition and treatment of IEI lung disease and improve outcome. The aim of this study was to compare multiple-breath washout (MBW) and spirometry in patients with IEI and cystic fibrosis (CF) as well as healthy controls (HC) and to evaluate the sensitivity of lung clearance index (LCI) to assess lung disease in IEI. Methods: IEI patients (n=114) were recruited from our paediatric and adult immunodeficiency outpatient clinics and compared to age-matched CF patients (n=114) and HC (n=114). MBW measurements and spirometry were performed in the study participants, and MBW testing was repeated after 63-707 days in IEI patients (n=70). Results: The LCI was significantly higher in IEI patients than in HC (p<0.001) and significantly lower than in CF patients (p<0.001). The forced expiratory volume in 1 s (FEV1) z-score was significantly lower in IEI patients than in HC (p<0.01) and significantly higher than in CF patients (p<0.01). LCI and FEV1 z-score correlated moderately negatively in the total cohort, the IEI group and the CF group. Nineteen (20.7%) of 92 IEI patients and 35 (33.3%) of 105 CF patients had an elevated LCI but a normal FEV1 z-score. After a median of 364 days, the median LCI of 70 IEI patients increased significantly by 0.2. Conclusion: MBW is useful to detect lung disease in IEI and is more sensitive than spirometry.

Body computed tomography in sepsis: predictors of CT findings and patient outcomes in a retrospective medical ICU cohort study.

BACKGROUND: Sepsis is a life-threatening condition that requires immediate focus identification and control. However, international sepsis guidelines do not provide information on imaging choice. PURPOSE: To identify predictors of CT findings and patient outcomes in a population of septic patients from a medical ICU. MATERIAL AND METHODS: A full-text search in the radiological information system (RIS) retrieved 227 body CT examinations conducted to identify infectious sources in 2018. CT reports were categorized according to identified foci and their diagnostic certainty. Diagnostic accuracy of CT was compared to microbiological results. Clinical and laboratory information was gathered. Statistical analysis was performed using nonparametric tests and logistic regression analysis. RESULTS: CT revealed more positive infectious foci 52.4% (n = 191/227) than microbiological tests 39.3% (n = 79/201). There were no significant differences between focus-positive CT scans with regard to positive microbiological testing (p = 0.32). Sequential organ failure assessment (SOFA) scores were slightly but nonsignificantly higher in patients with a focus-positive CT, odds ratio (OR) = 0.999 (95% CI 0.997-1.001) with p = 0.52. Among C-reactive protein (CRP), procalcitonin (PCT), and leukocytes, in focus-positive versus focus-negative CT scans, CRP showed a minor but statistically significant elevation in the group with focus-positive CT scans (OR = 1.004, 95% CI = 1.000-1.007, p = 0.04). No significant association was found for PCT (OR = 1.007, 95% CI = 0.991-1.023; p = 0.40) or leukocytes (OR = 1.003, 95% CI = 0.970-1.038; p = 0.85). In 33.5% (n = 76/227) of cases, the CT findings had at least one therapeutic consequence. In 81.6% (n = 62/76), the CT findings resulted in one consequence, in 14.5% (n = 11/76) in two consequences, and in 3.9% (n = 3/76) in three consequences. There was no significant association between focus-positive CT scans and mortality (p = 0.81). CONCLUSION: In this population of septic patients in medical intensive care, microbiological analysis complemented CT findings. Both clinical and laboratory parameters were not predictive of CT findings. While therapeutic consequences of CT findings in this study population underline the role of CT for decision making in septic patients, CT findings do not predict patient outcomes in this retrospective analysis.