Article Unexpected analytical interference in isavuconazole UV determination in a child in therapy with lumacaftor/ivacaftor for cystic fibrosis was published on November 1, 2019 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 57, issue 11).

Low plasma concentrations of docosahexaenoic acid (DHA) are reported in unsupplemented cystic fibrosis (CF) patients. Forty-one CF patients aged from 6 to 12 years were randomized to receive high-dose DHA (100 mg/kg/day in the first month and 1g per day thereafter through a 12-month supplementation) or placebo (germ oil). Primary outcome was percentage change in plasma AA:DHA ratio. Secondary outcomes were changes in the number of pulmonary exacerbations compared to previous year, lung function, BMI, skinfold thicknesses, and body composition assessed by DXA and in serum concentrations of C-reactive protein, cytokines and vitamin (α-tocopherol and retinol). Compared to the control group plasma AA:DHA ratio decreased in the intervention group after 6 months (median percentage changes: -73% in the intervention group vs. -10% in the control group, P=0.001). No differences were detected between groups for secondary outcomes. Despite a decrease of the AA/DHA ratio, DHA supplementation for one year did not induce any significant biochemical and clinical improvement in CF patients.

Cystic Fibrosis (CF) lung disease is characterized by high levels of cytokines and chemokines in the airways, producing chronic inflammation. Non-invasive biomarkers, which are also specific for the inflammatory and immune responses, are urgently needed to identify exacerbations and evaluate therapeutic efficacy. The aim of this study is to evaluate the association of sputum and exhaled breath condensate (EBC) biomarker changes with clinical exacerbation and response to therapy. We studied the simultaneous presence and concentration of twelve cytokines and growth factors (EGF, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, MCP-1, TNF-α and VEGF) by a multi-parametric biochip array in sputum and EBC of 24 CF patients before, after 6 and 15 days of therapy, and 15 days after the end of treatment for an acute exacerbation. Correlations with functional respiratory tests (FEV 1 , FVC) and the systemic marker C-reactive protein (CRP) were looked for. In sputum, before therapy, VEGF and IL-1β levels positively correlated with the respiratory function and CRP. Sputum IL-1α, IL-1β IL-4, IL-10, TNF-α, and VEGF significantly decreased, while EGF increased, during therapy. IL-8 and IL-4 levels negatively correlated with the respiratory function at 15 and 30 days from the start of therapy, respectively. IL-4, IL-6, IL-10 and TNF-α positively correlated with CRP during therapy. Although some EBC biomarkers correlated with respiratory function and CRP, no significant associations with these clinical parameters were found. Sputum IL-1β and VEGF might be considered biomarkers of an acute exacerbation in CF patients. A panel of sputum cytokines and growth factors may better describe the response to intravenous antibiotic treatment of CF than one single systemic marker.

Background: A. xylosoxidans (Ax) is capable of persistent infection of the respiratory tract of Cystic Fibrosis patients although its contribution to pulmonary decline in this population is not clear.Aim: To evaluate pathogenic role of Ax studying lung function and nutritional status in CF patients with chronic Ax infection.Methods: Data (FEV1, FVC, BMI, sputum and number of IV therapy) of 20 CF patients in follow-up at our centre were studied retrospectively at the time of establishment of infection (T0), one year before (T-1) and one year after (T+1) and were then compared.Statistical analysis was performed by Student's T test.Mean age of the 20 (13 females) patients was 14.5 (range 6.2-23.3)at T0. Results: Lung function showed a slight decrease in the year before the acquisition of Ax both in FVC (91.2±20.4vs 86.1±12.6%/predictedp = 0.22) and FEV1 (84.4±20.5 vs 79.1±16.3%/predicted p = 0.09), without reaching statistical significance.Respiratory data showed no deterioration in the year after infection: FVC (88.4±18.1 vs 86.1±12.6%/predictedp = 0.47) and FEV1 (82.9±23.2vs 79.1±16.3%/predicted p = 0.26).However, the number of respiratory exacerbations was much higher in the year after colonisation as demonstrated by the i.v.treatment mean days per patient (12.1±15.5 vs 3.1±6.5,p = 0.03).Nutritional status remained unchanged during the study period as demonstrated by BMI of T-1 vs T0 (18.1±2.9 vs 18.1±3.1 p = 0.77) and T0 vs T+1 (18.1±3.1 vs 18.7±2.9p = 0.07). Conclusion:The pathogenic role of chronic infection by Ax seems to be relevant in terms of therapeutic burden for patients in the short-term.A key factor would be monitoring the evolution of the patients chronically infected by Ax.

Background: The aim of this study of 352 patients, 1–14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences. Methods: The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates. Results: Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria. Conclusions: Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.

This paper reports the data concerning the net economic cost savings attributable to influenza vaccination in healthy children aged 2-5 years, and may be useful when deciding the best recommendations for the use of influenza vaccine in pediatrics. A total of 303 previously unprimed healthy children aged 2-5 years (163 males; mean age +/- S.D.: 3.22 +/- 2.43 years) were prospectively, blindly randomised in a 2:1 ratio to receive two doses of an inactivated, trivalent, virosome-formulated subunit influenza vaccine (Inflexal V, Berna Biotech, Berne, Switzerland) or no vaccination. The results show that influenza vaccination of healthy children aged 2-5 years Substantially reduces influenza-like illnesses and related costs in the children themselves and their families. However, larger and longer running study spanning multiple seasons may be warranted before Suggesting the universal vaccination of this group Of Subjects. (c) 2005 Elsevier Ltd. All rights reserved.

In order to establish the role of atypical bacteria and compare characteristics of different infectious agents in acute pharyngitis, 127 patients with acute pharyngitis (66 males; median age, 5.33 years; range, 6 months to 14 years) and 130 healthy subjects of similar sex and age were studied. Serology with paired samples and PCR on nasopharyngeal aspirates and throat cultures were used to identify bacteria and viruses. Viruses were identified in 43 patients (33.8%) and five controls (3.8%; P<0.0001), potential bacterial pathogens in 34 patients (26.8%) and 26 controls (20%; P=0.256) and mixed viral/bacterial pathogens in 26 patients (20.5%) and none of the controls (P<0.0001). The main aetiological agents were adenovirus, respiratory syncytial virus (RSV), Mycoplasma pneumoniae, Streptococcus pyogenes and Chlamydia pneumoniae. M. pneumoniae was the agent found most frequently as a single pathogen. A history of recurrent pharyngitis, having older siblings and a negative outcome were significantly more common among patients with acute M. pneumoniae infection than among those with infections due to other pathogens or healthy controls. This study demonstrates that: (i) adenovirus and RSV have a prominent role in acute pharyngitis; (ii) S. pyogenes is found frequently, but it is not possible to distinguish simple carriers from patients with a true infection; (iii) M. pneumoniae appears to be able to cause acute pharyngitis per se; and (iv) C. pneumoniae seems to be mainly a co-pathogen. To avoid the risk of an incorrect therapeutic approach, simple laboratory investigations that allow rapid identification of M. pneumoniae infections are urgently needed.