Epidemiologic Study of Cystic Fibrosis: 25 years of observational research.

The Epidemiologic Study of Cystic Fibrosis (ESCF) was a prospective observational study of over 32,000 people with cystic fibrosis (CF) from 250 clinical care sites in North America from 1994 to 2005. Begun as a pharmacovigilance study in connection with the approval of dornase alfa in 1993, ESCF was open to all people with CF treated at any participating site in the United States or Canada. In addition to obtaining safety and effectiveness data on dornase alfa, ESCF collected encounter-based data to characterize the natural history and management of CF with a special focus on lung disease.

Lung function changes before and after pulmonary exacerbation antimicrobial treatment in cystic fibrosis.

Background: In cystic fibrosis, observation of a lung function drop (as percent predicted forced expiratory volume in 1 s [FEV ]; ppFEV ) frequently precedes pulmonary exacerbation (PEx) diagnosis. Recovery of ppFEV to a previous "baseline" is commonly used to assess antimicrobial treatment response. However, not all diagnosed PEx are associated with a ppFEV drop, and it is unclear whether these are a different type of PEx from those associated with a ppFEV drop.

Pulmonary exacerbations and acute declines in lung function in patients with cystic fibrosis.

Background: Patients with cystic fibrosis (CF) who experience acute declines in percent predicted FEV (ppFEV decreased ≥10% relative to baseline) are often not treated with antibiotics for pulmonary exacerbations (PEx), whereas other patients are treated even when they have not experienced a decline in lung function.

Methods: We analyzed 2 patient cohorts using 3 years of Epidemiologic Study of CF data. Cohort 1 (12,837 patients) experienced a ≥10% acute decline in ppFEV (n = 22,898) and Cohort 2 (10,416 patients) had a clinician-diagnosed PEx (n = 20,731).

Lung function decline is delayed but not decreased in patients with cystic fibrosis and the R117H gene mutation.

Background: Patients with cystic fibrosis (CF) experience variable lung disease phenotypes. The R117H mutation is often associated with preserved lung function. Our objective was to compare the rate of lung function decline in patients with the R117H mutation and patients homozygous for the F508del mutation.

Comparison of FEV reference equations for evaluating a cystic fibrosis therapeutic intervention.

Objectives: The Global Lung Function Initiative (GLI, 2012) developed reference equations for forced expiratory volume in 1 s (FEV ). Previous equations were developed by groups led by Knudson (1983), Wang (1993), Hankinson (1999), and Stanojevic (2008). We assessed how different prediction equations affect the conclusions from a therapeutic intervention study that evaluated the rate of percent predicted FEV (ppFEV ) decline.

Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor.

Background: Pulmonary exacerbations (PEx) are associated with acute loss of lung function that is often not recovered after treatment. We investigated lung function recovery following PEx for ivacaftor- and placebo-treated subjects.

Methods: Short- and long-term pulmonary function recovery data after PEx were summarized from a placebo-controlled trial in 161 cystic fibrosis patients≥12years old with the G551D-CFTR mutation (NCT00909532).

Strengthening care teams to improve adherence in cystic fibrosis: a qualitative practice assessment and quality improvement initiative.

Background: Treatment regimens for patients with cystic fibrosis (CF) are complex, time consuming, and burdensome, and adherence to CF treatment is suboptimal. CF care teams play a critical role in supporting patients' chronic self-management skills, but there is no uniform method for assessing patients' adherence to treatment or standard interventions to help patients improve when necessary.

Methods: Between May 2015 and March 2016, care team members from 10 CF centers in the USA participated in a practice assessment and quality improvement (QI) initiative.

Relationship of Antibiotic Treatment to Recovery after Acute FEV Decline in Children with Cystic Fibrosis.

Rationale: Children with cystic fibrosis often experience acute declines in lung function. We previously showed that such declines are not always treated with antibiotics, but we did not assess whether treatment improves the likelihood of recovery.

Objectives: To determine whether new antibiotic treatment was associated with recovery from acute FEV decline.

Frequency and costs of pulmonary exacerbations in patients with cystic fibrosis in the United States.

Background: Information is limited regarding the cost of pulmonary exacerbations (PEx) among patients with cystic fibrosis in the United States.

Methods: To examine PEx costs, medical chart data were linked to insurance claims for patients aged ≥6 years who had commercial coverage from a large US health insurer affiliated with Optum during 2008-2013. A PEx was categorized as an episode requiring newly started (1) oral antibiotics (PEx-O) or (2) intravenous (IV) antibiotics and/or inpatient stay (PEx-IV).

BMI fails to identify poor nutritional status in stunted children with CF.

Background: Body mass index (BMI) is currently emphasized for evaluating nutritional status in children with cystic fibrosis (CF). Weight for age (WFA) and height for age (HFA) may get less attention.

Methods: Data from the Epidemiologic Study of Cystic Fibrosis were used to compare patient WFA, HFA, and BMI percentiles for children age 2 to 18years.

Improving performance in the detection and management of cystic fibrosis-related diabetes in the Mountain West Cystic Fibrosis Consortium.

Objective: Cystic fibrosis (CF)-related diabetes (CFRD) is associated with increased morbidity and mortality. Improved detection and management may improve outcomes; however, actual practice falls short of published guidelines. We studied efforts to improve CFRD screening and management in the Mountain West CF Consortium (MWCFC).

Healthcare resource utilization associated with ivacaftor use in patients with cystic fibrosis.

Objective: Ivacaftor was approved in 2012 to treat patients with cystic fibrosis (CF) with specific CFTR gene mutations. The objective of this analysis was to analyze the impact of ivacaftor on health resource utilization through analysis of claims data.

Methods: Patients diagnosed with CF aged ≥6 years prescribed ivacaftor between January 1, 2012 and July 31, 2014 with ≥12 months of continuous insurance coverage prior to and following the prescription were identified.

Forced Expiratory Volume in 1 Second Variability Helps Identify Patients with Cystic Fibrosis at Risk of Greater Loss of Lung Function.

Objective: To evaluate several alternative measures of forced expiratory volume in 1 second percent predicted (FEV1 %pred) variability as potential predictors of future FEV1 %pred decline in patients with cystic fibrosis.

Study Design: We included 13,827 patients age ≥6 years from the Epidemiologic Study of Cystic Fibrosis 1994-2002 with ≥4 FEV1 %pred measurements spanning ≥366 days in both a 2-year baseline period and a 2-year follow-up period. We predicted change from best baseline FEV1 %pred to best follow-up FEV1 %pred and change from baseline to best in the second follow-up year by using multivariable regression stratified by 4 lung-disease stages.

Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data.

Rationale: In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate comparator population.

Objectives: To examine, over a 3-year period, whether ivacaftor therapy affects pulmonary function and nutritional measures in patients with CF with a G551D mutation compared with patients with CF who are homozygous for the F508del mutation.

Liver involvement in the Hispanic population of North America with cystic fibrosis.

Objectives: The aim of the present article was to determine the prevalence of liver involvement in Hispanic patients with cystic fibrosis (CF) and identify associations with age and severity of liver involvement.

Methods: We used 1994-2005 Epidemiologic Study of CF data to compare abnormal liver findings between Hispanic and non-Hispanic white patients with CF.

Results: Of 30,727 patients with CF, 5015 had liver involvement.

Pulmonary capillaritis in monozygotic twin boys.

Pulmonary hemorrhage can be classified as either proximal or distal (alveolar). Causes of proximal hemorrhage include infection, foreign body aspiration, pulmonary embolus, trauma, vascular malformation, and pulmonary hypertension. Causes of distal or diffuse alveolar hemorrhage are divided by the histologic presence or absence of capillaritis, which is characterized by inflammation of the alveolar interstitium and pulmonary capillary structure.

Clinical use of tobramycin inhalation solution (TOBI®) shows sustained improvement in FEV1 in cystic fibrosis.

Objectives: Tobramycin inhalation solution (TIS; TOBI®) has improved forced expiratory volume in 1 sec (FEV1 ) in cystic fibrosis (CF) trials. Using data from the Epidemiologic Study of CF (ESCF), we assessed the change in level and trend of FEV1 % predicted (pred) over a 2-year period associated with initiation of TIS during routine clinical practice.

Methods: Patients age 8-38 years and in ESCF for ≥2 years before treatment with TIS as a chronic therapy were selected if they remained on therapy for 2 years, defined as being on TIS for at least 3 months per year (C-TIS group).

Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

Objective: To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1.

Study Design: Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture.

Dornase alfa (Pulmozyme).

Purpose Of Review: Dornase alfa (Pulmozyme) is one of the most commonly used medications to treat the lung disease of cystic fibrosis (CF). As other respiratory medications have entered the clinical market, understanding the proper use and indication for dornase alfa is increasingly important. In addition, dornase alfa is being used to treat other medical conditions.

Pulmonary exacerbations in cystic fibrosis: young children with characteristic signs and symptoms.

Background: A standard definition of pulmonary exacerbation based on signs and symptoms would be useful for categorizing cystic fibrosis (CF) patients and as an outcome measure of therapy. The frequently used definition of treatment with intravenous antibiotics varies with practice patterns. One approach to this problem is to use large data sets which include a patient's signs and symptoms along with their clinician's decision to treat with antibiotics for the diagnosis of pulmonary exacerbation.

Oral, inhaled, and intravenous antibiotic choice for treating pulmonary exacerbations in cystic fibrosis.

Rationale: Patients with cystic fibrosis (CF) experience frequent pulmonary exacerbations (PExs). Clinicians manage these episodes of worsening signs and symptoms in a variety of ways.

Objectives: To characterize the antibiotic management and associated change in lung function following PExs.

Risk factors for rate of decline in FEV1 in adults with cystic fibrosis.

Background: Previously we assessed risk factors for FEV(1) decline in children and adolescents using the Epidemiologic Study of Cystic Fibrosis (J Pediatr 2007;151:134-139); the current study assessed risk factors in adults.

Methods: Risk factors for FEV(1) decline over 3-5.5 years for ages 18-24 and ≥25 years were assessed using mixed-model regression.