Pulmonary exacerbations, airway pathogens, and long-term course of lung clearance index in children and young adults with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations (PEx), pathogens colonizing the respiratory tract, and patients' age are associated with progressive worsening of lung function among patients with cystic fibrosis (CF). However, the effect of these factors on longitudinal changes of Lung Clearance Index (LCI) remains unclear. AIM: To assess the role of age, different types of bronchial infection, and PEx on LCI deterioration. METHODS: We conducted a retrospective study assessing multiple-breath washout (MBW) and spirometry changes among CF patients evaluated at quarterly outpatient clinic visits over 8 years. MBW and spirometry were performed at each visit, sputum samples and/or cough swabs were obtained for culture, whereas respiratory symptoms and clinical examination findings were recorded. Patients who had ≥5 serial MBW measurements, one of which coincided with a pulmonary exacerbation, were reviewed. RESULTS: Seventy-six patients were included in the study: mean age of 10.61 years (range 1.75-23.75). A total of 1152 MBW tests and 1047 spirometry tests were performed. LCI was significantly higher among CF patients aged 11-15, 16-20, and over 20 years than those under 5 years of age; ΔLCI: 1.16 (confidence interval [CI] 0.43-1.90) and 3.25 (CI 2.33-4.17), respectively. Furthermore, LCI was significantly elevated in CF patients with positive cultures for Pseudomonas aeruginosa (0.52 LCI [CI -0.12 to 0.71]) and Stenotrophomonas Maltophilia (1.41 LCI [CI 0.61-2.21]). Moreover, increased values of LCI in CF patients were significantly associated with increased risk of PEx (odds ratio [OR] 1.19, CI [1.14-1.25], p < 0.001). CONCLUSION: LCI demonstrates a progression of lung disease and corresponds to changes in bacterial infections and PEx among patients with CF. LCI may be a valuable marker for tracking disease deterioration and may have a role in the routine clinical care of patients with CF.

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.

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study.

BACKGROUND: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta2-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years. OBJECTIVE: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age. METHODS: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records. RESULTS: The children had previously received short-acting ß2-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group. CONCLUSIONS: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.

A Case Report of Pulmonary Exacerbation after Initiation of Lumacaftor/Ivacaftor Therapy in a CF Female with Complicated Lung Disease.

Novel targeted treatments for Cystic Fibrosis give rise to new hope for an ever-growing number of CF patients with various mutations. However, very little evidence and guidelines exist to steer clinical decisions regarding patients whose illness takes an unexpected course. In such cases, the benefits and risks of discontinuing these treatments must be carefully and individually weighed, since their long-term effects remain mainly uncharted territory. In this report we document the case of a homozygous F508del CF patient with severe lung disease who presented with a pulmonary exacerbation shortly after the beginning of treatment with lumacaftor/ivacaftor and the complicated initial phase of therapy, which was followed by significant improvements.

A "real-life" study on height in prepubertal asthmatic children receiving inhaled steroids.

INTRODUCTION: Asthma is the most common chronic respiratory disease in children and inhaled corticosteroids (ICS) constitute the first line of treatment for these patients. However, the potential growth-inhibiting effect of ICS has often been a cause of concern for both caregivers as well as physicians, and there still remains conflict regarding their safety profile. OBJECTIVE: To assess whether the administration of ICS in low or medium doses is associated with height reduction in prepubertal children. METHODS: We performed a retrospective study to examine the association between ICS treatment and growth deceleration in children with mild persistent asthma. The comparison of height measurements every 6 months from 3 to 8 years of age was conducted among three groups of patients: patients not receiving ICS, patients being treated with low dose of ICS and patients being treated with medium dose of ICS (GINA Guidelines 2015). RESULTS: This study included 284 patients (198 male, 86 female) aged 3-8 years; 75 patients were not receiving ICS, 63 patients were on low-dose ICS and 146 patients were on medium-dose ICS. The measured height every 6 months did not differ significantly (p > 0.05) among the three groups while the difference remained stable (p > 0.05), even when we evaluated males and females separately. CONCLUSIONS: In this "real-life" study we found that long-term treatment with ICS in low or medium doses is not associated with height reduction in prepubertal children with asthma.