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.

Low-frequency oscillometry indices to assess ventilation inhomogeneity in CF patients.

BACKGROUND: The utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower-frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity. METHODS: Forty-five children, adolescents, and adults with CF (age 6.9-27 years) underwent spirometry, FOT, and nitrogen multiple-breath washout (N2-MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity. RESULTS: The sGrs correlated well with the lung clearance index (LCI) (Spearman's r: -.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and -.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices. CONCLUSIONS: In CF patients, the FOT indices at 5 Hz and the novel, volume-adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2-MBW. Future research should explore the role of lower-frequency FOT in assessing the severity and monitoring the progression of CF lung disease.

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.

Toward the Establishment of New Clinical Endpoints for Cystic Fibrosis: The Role of Lung Clearance Index and Cardiopulmonary Exercise Testing.

As Cystic Fibrosis (CF) treatment advances, research evidence has highlighted the value and applicability of Lung Clearance Index and Cardiopulmonary Exercise Testing as endpoints for clinical trials. In the context of these new endpoints for CF trials, we have explored the use of these two test outcomes for routine CF care. In this review we have presented the use of these methods in assessing disease severity, disease progression, and the efficacy of new interventions with considerations for future research.

Validation study of the pediatric allergic rhinitis quality of life questionnaire.

BACKGROUND: The Paediatric Allergic Rhinitis Quality of Life Questionnaire (Ped-AR-QoL) is the first tool developed for the assessment of health-related quality of life (QoL) in Greek children with allergic rhinitis (AR). OBJECTIVE: The aim of the current study was to validate the child and parent forms of the Ped-AR-QoL in children aged 6-14 years-old who suffered from AR and were followed in a pediatric allergy clinic. METHODS: The Ped-AR-QoL, which was completed by 112 children and their parents, was correlated to the generic QoL questionnaire (Disabkids), which is already valid in Greece for children with chronic disorders, as well as with expert opinions on the severity of disease. RESULTS: The Ped-AR-QoL child and parent forms had very good internal consistency (α values of 0.797 and 0.872, respectively), while there was a moderate positive correlation of the disease-specific questionnaire with most of the subscales of the generic questionnaire. There has been a statistically significant association between the Ped-AR-QoL and the expert perception of disease severity. CONCLUSIONS: The Ped-AR-QoL had very good reliability and convergent validity when compared with the generic Disabkids QoL. The significance of the association between the disease-specific questionnaire and the expert opinion is an important finding validating the questionnaire. The Ped-AR-QoL may become a helpful tool which can be used in everyday clinical practice by clinicians and it may also be used for assessing therapeutic interventions in clinical trials.

A Rare Case of Clavicle Osteomyelitis in a Child and Literature Review.

Acute clavicle osteomyelitis in children is rare representing <3% of osteomyelitis cases. We treated a 12-year-old boy who presented with acute pain in the right clavicle and high fever for 4 days. MRI showed abnormal signal in the right clavicle with periosteal reaction. Staphylococcus aureus isolated from blood was susceptible to methicillin, clindamycin, and macrolides. Clindamycin was given intravenously for 3 wks and orally for another 3 wks with no recurrence. We reviewed clavicle osteomyelitis cases in children searching PubMed English literature. From a total of 89 studies retrieved, only 6 fulfilled the criteria and were analyzed. Sixteen patients (56% female) were included with a median age of 9 yrs (range 2 wks-16 yrs). Osteomyelitis was hematogenous in most cases, with S. aureus being the most frequent cause, isolated from either blood or tissue. Symptoms included fever, swelling, and localized bone tenderness. Antimicrobial therapy lasted for 4-12 weeks (median 7.5). Three patients required drainage or curettage. Recurrence occurred in 1/16 cases (6.2%) and persistence of symptoms occurred to 2/16 cases (12.5%) reported before 90s with unknown antimicrobial susceptibility of the pathogen. Acute clavicle osteomyelitis mainly affects older children and has generally good prognosis. Staphylococcus aureus is most commonly implicated and surgery may be needed.