Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

BACKGROUND: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. METHODS: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. RESULTS: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). CONCLUSIONS: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials

Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis

The optimal strategy for monitoring cystic fibrosis (CF) lung disease in infancy remains unclear

Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial.

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 3× weekly with standardized TIS. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. CONCLUSIONS: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156)

Multicenter Evaluation of Infant Lung Function Tests as Cystic Fibrosis Clinical Trial Endpoints

Rationale: The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures

Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis

BACKGROUND: The optimal strategy for monitoring cystic fibrosis (CF) lung disease in infancy remains unclear. OBJECTIVE: To describe longitudinal associations between infant pulmonary function tests (iPFTs), chest radiograph (CXR) scores and other characteristics. METHODS: CF patients ≤ 24 months old were enrolled in a 10-center study evaluating iPFTs 4 times over a year. CXRs ~1 year apart were scored with the Wisconsin and Brasfield systems. Associations of iPFT parameters with clinical characteristics were evaluated with mixed effects models. RESULTS: The 100 participants contributed 246 acceptable flow/volume (FEV(0.5), FEF(75)) and 303 acceptable functional residual capacity (FRC) measurements and 171 CXRs. Both Brasfield and Wisconsin CXR scores worsened significantly over the 1 year interval. Worse Wisconsin CXR scores and S. aureus were both associated with hyperinflation (significantly increased FRC) but not with diminished FEV(0.5) or FEF(75). Parent-reported cough was associated with significantly diminished FEF(75) but not with hyperinflation. CONCLUSIONS: In this infant cohort in whom we previously reported worsening in average lung function, CXR scores also worsened over a year. The significant associations detected between both Wisconsin CXR score and S. aureus and hyperinflation, as well as between cough and diminished flows, reinforce the ability of iPFTs and CXRs to detect early CF lung disease

Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap. An Official American Thoracic Society Workshop Report.

A workshop Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap was held at the American Thoracic Society 2019 International Conference. Interoperability is defined as is the ability of different information-technology systems and software applications to directly communicate, exchange data, and use the information that has been exchanged. At present, pulmonary function test (PFT) equipment is not required to be interoperable with other clinical data systems, including electronic health records (EHRs). For this workshop, we assembled a diverse group of experts and stakeholders, including representatives from patient-advocacy groups, adult and pediatric general and pulmonary medicine, informatics, government and healthcare organizations, pulmonary function laboratories, and EHR and PFT equipment and software companies. The participants were tasked with two overarching Aobjectives: 1) identifying the key obstacles to achieving interoperability of PFT systems and the EHR and 2) recommending solutions to the identified obstacles. Successful interoperability of PFT data with the EHR impacts the full scope of individual patient health and clinical care, population health, and research. The existing EHR-PFT device platforms lack sufficient data standardization to promote interoperability. Cost is a major obstacle to PFT-EHR interoperability, and incentives are insufficient to justify the needed investment. The current vendor-EHR system lacks sufficient flexibility, thereby impeding interoperability. To advance the goal of achieving interoperability, next steps include identifying and standardizing priority PFT data elements. To increase the motivation of stakeholders to invest in this effort, it is necessary to demonstrate the benefits of PFT interoperability across patient care and population health