Use of cystic fibrosis inhaled medication before and after elexacaftor/tezacaftor/ivacaftor initiation.

Elexacator/tezacaftor/ivacaftor (ETI) has improved cystic fibrosis (CF) outcomes. A reduction in use of maintenance medication after its initiation has been reported. Seventy-one adult people with CF (PwCF) who are followed in three CF centers and completed one year of treatment with ETI were included in this study. Their use of inhaled dornase-α, colistin, tobramycin, aztreonam and levofloxacin during this period was compared with the corresponding use during one year without ETI, using the Medication Possession Ratio (MPR). MPR was significantly decreased after ETI initiation for dornase-α (67±35% vs 48±40%, p<0.001) and for all four inhaled antibiotics together (62±33% vs 41±37%, p<0.001). The findings of this multi-center, retrospective, study suggest that the initiation of ETI significantly leads to decrease in use of standard inhaled medication in PwCF. The significance of this finding in the course of the disease is yet to be investigated by larger prospective clinical trials.

Pulmonary medication adherence among children and adults with cystic fibrosis: Is there an association with disease severity?

BACKGROUND: Adherence to pulmonary medication is pivotal in delaying the progression of lung disease in cystic fibrosis (CF). Further exploring the consequences of poor adherence and its impact on disease severity may be valuable to personalize CF treatment strategy. AIM: To evaluate indicators of disease severity among children and adults with CF and investigate which of them are related to pulmonary medication adherence. METHODS: This is a retrospective cohort study. Data of children and adults followed up in one pediatric and one adult CF Unit were evaluated over 4 years. Disease severity was assessed by measuring body mass index (BMI), lung function, history of pulmonary exacerbations, and medication complexity. Adherence was assessed by calculating a 12-month medication possession ratio (MPR) for each pulmonary medication and then averaged for a composite MPR (cMPR) for each patient. Regression analysis was performed to explore the association of adherence with disease severity. RESULTS: Ninety-five patients were included in our study, 52 children and 43 adults. The overall cMPR was 0.74 (SD = 0.25); 0.68 (SD = 0.24) for children and 0.81 (SD = 0.24) for adults. Adults presented higher adherence, with overall mean cMPR 0.81 (SD = 0.24) compared to children with mean cMPR 0.68 (SD = 0.24) (p < 0.05, 95% CI = -0.27 to -0.03). Adherence was inversely related to FEV1 % predicted (ß = -0.002, 95% CI = -0.004 to 0, p = 0.023) and FVC% predicted (ß = -0.003, 95% CI = -0.005 to -0.001, p = 0.006) in regression analysis. Adherence was not found to be associated with BMI, history of exacerbations and medication complexity. The analysis of each medication showed that adherence to Dornase-alpha, Tobramycin and Colomycin was significantly related to specific disease severity indicators. CONCLUSION: An overall moderate to high level of adherence was found among our study population. Adults presented higher adherence compared to children. FEV1% and FVC% predicted were related to a significant decrease in adherence. Among our group of CF patients with an overall moderate to high level of adherence, adherence to pulmonary medication was inversely related to disease severity.

Adherence to inhaled therapies over 4 years in people with cystic fibrosis.

BACKGROUND: This study examined the drug-specific and overall adherence of teenagers and adults with cystic fibrosis (CF) to inhaled therapies, to assess the degree of adherence, stability over a period of 4 years, and its association with health outcomes. METHODS: Fifty-five participants (30 women and 25 men) aged 14 years or older from two CF centers were enrolled in a retrospective review of inhaled medication adherence over 4 years. Adherence was assessed by the number of doses that were obtained by each participant based on the "e-prescription.gr" platform and the calculation of the medication possession ratio (MPR). RESULTS: The mean composite MPR (cMPR) for the entire research period was 0.75 ± 0.19. A total of 43.4% of participants showed a variance of adherence <25%. Participants with stable adherence had a significantly higher mean cMPR compared with those with variable adherence (0.86 ± 0.16 vs. 0.66 ± 0.17, p < 0.001). A statistically significant difference between groups of patients with different degrees of mean cMPR and mean weight was observed (p = 0.011). Patients with a mean cMPR ≥0.80 weighed significantly more than those with moderate and low adherence. In addition, mean weight correlated significantly with the mean cMPR (Β [95% confidence interval] = 14.845 [0.191-29.498], r = 0.269, p = 0.047). CONCLUSIONS: In our setting, the cMPR was easy to assess and showed that adherence was probably better than expected. The association of cMPR with weight should be further investigated. Stable adherence seemed to be related to high adherence. This observation could enhance our understanding of people with CF and their approach to treatment.

Severe Pulmonary Disease Caused by Mycolicibacter kumamotonensis.

Severe Mycolicibacter kumamotonensis-pulmonary disease was diagnosed in a 68-year-old immunocompetent woman in Greece; the disease was initially treated as tuberculosis. The patient responded favorably to a new treatment regimen of azithromycin, amikacin, moxifloxacin, and linezolid. Complete symptom resolution and radiologic improvement resulted.

Moxifloxacin in Chronic Obstructive Pulmonary Disease: Pharmacokinetics and Penetration into Bronchial Secretions in Ward and Intensive Care Unit Patients.

This study aimed to evaluate the pharmacokinetic profile of moxifloxacin (MXF) in serum and sputum/bronchial secretions of 22 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the ward and intensive care unit (ICU). The data showed that ICU patients had lower concentrations in secretions (P = 0.01). However, no other statistically significant differences were observed in pharmacokinetic parameters and penetration in secretions between ward and ICU patients. MXF showed a favorable pharmacokinetic profile, and the pharmacodynamic targets for common pathogens for AECOPD were achieved.

Is daily exposure to ozone associated with respiratory morbidity and lung function in a representative sample of schoolchildren? Results from a panel study in Greece.

Previous time series or panel studies of asthmatics have reported respiratory health effects following short-term exposure to ozone (O3). We followed 186 children aged 10 years old in Athens and Thessaloniki, Greece for 5 weeks during the academic year 2013-2014 and recorded daily their respiratory symptoms, absenteeism and peak expiratory flow (PEF). We applied mixed models controlling for various possible confounders to investigate the daily associations between O3 exposure - derived from weekly personal and fixed school site measurements calibrated using daily values of the fixed monitoring site nearest to the child's school location - and PEF, presence of any symptom, cough and stuffy nose, as well as absenteeism. We tested the robustness of our findings to varying modeling assumptions and confounders and investigated effect modification patterns by medication use, time spent outdoors and prevalence of asthma. A 10 µg/m3 increase in O3 personal exposure was associated with increased odds of any symptom (odds ratio (OR): 1.19, 95% confidence interval (CI): 0.98, 1.44), largely attributed to the increase in the odds of stuffy nose (OR: 1.23, 95% CI: 1.00, 1.51). PEF and absenteeism were not related to O3 exposure. Our results were robust to several sensitivity analyses. Effects were modified by medication use as presence of symptoms but also decreases in PEF were mainly reported among non-users, while our effect estimates were not driven by the asthmatic subgroup of children. Our findings indicate that short-term O3 exposure may be associated with respiratory symptoms extending previously reported results for asthmatics to the general population.

Pharmacokinetics of moxifloxacin and high-dose levofloxacin in severe lower respiratory tract infections.

This study evaluated the pharmacokinetics of intravenous moxifloxacin 400 mg once and levofloxacin 500 mg twice daily in patients with lower respiratory tract infections (LRTIs) and assessed their pharmacodynamic adequacy against common respiratory pathogens. Eighteen patients with LRTIs hospitalised in general wards were included. Serial blood samples were obtained at steady state and concentrations were determined using HPLC. Pharmacokinetic variables were estimated by a two-compartment model. The characteristic pharmacodynamic parameter for fluoroquinolones (AUC(0-24)/MIC) was calculated. Peak and trough concentrations were, respectively, 4.81 ± 1.03 and 0.59 ± 1.13 mg/L for moxifloxacin and 6.42 ± 1.08 and 0.79 ± 0.39 mg/L for levofloxacin. Pharmacokinetic data for moxifloxacin and levofloxacin, respectively, were: CL, 10.27 ± 1.24 and 22.66 ± 6.62 L/h; t1/2, 13.43 ± 5.12 and 6.75 ± 1.34 h; Vss, 163.03 ± 53.88 and 170.73 ± 39.59 L; and AUC(0-24), 39.38 ±5.28 and 47.06 ± 14.09 mg·h/L. The pharmacodynamic target was attained in all patients by both antibiotics against the majority of respiratory pathogens. Moxifloxacin proved to be pharmacodynamically efficacious against Gram-positive bacteria with MICs ≤ 0.79 mg/L and Gram-negative bacteria with MICs ≤ 0.32 mg/L. These MIC thresholds for levofloxacin were 1.1 mg/L and 0.38 mg/L, respectively. Moxifloxacin and high-dose levofloxacin show a favourable pharmacokinetic profile in plasma of patients with severe LRTIs, without significant interpatient variability. They ensure optimal pharmacodynamic exposure against the majority of microbes involved in these infections. However, the predicted efficacy against Gram-negative bacteria with MICs ≥ 0.5 mg/L appears to be low.