Changes in Lung Function Based on Differences in Spirometry Equipment Used in Children With Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive genetic disease, characterized by pulmonary and sinus disease, gastrointestinal and reproductive tract dysfunction. CF patients suffer from chronic repeated cycles of pulmonary bacterial infection, pulmonary exacerbations and chronic lung function decline, which often lead to premature death. Although improved treatment of lung disease has increased survival, the median predicted age for survival is only 37.2 years in the United States (US) (CFF Annual Data Report, 2008) and patients continue to have significant morbidity, including hospitalizations (Ramsey, 1996).

Pulmonary Function Tests (PFTs) are used to measure and track lung health of patients with CF. Performing a PFT takes practice and requires patients to perform certain breathing maneuvers consistently. Infants and young children cannot be tested using spirometers. The investigators start PFT training with our patients after they reach 4 years of age. It may take several months to a few years for useful, consistent and interpretable PFTs to be obtained. According to standards developed by the American Thoracic Society, children must be able to breathe in very deeply, exhale fast and hard, and continue exhaling for several seconds. Children also must perform these maneuvers in a repeatable manner. (Ferris, 1978 ). Recent software programs have been developed to encourage and assist children in completing the breathing maneuvers. Videogame-like graphics respond to children's efforts. Children can often choose which "game" to play, such as, "Blow out the candles."

PFT results have taken on greater importance as new therapies are tested and evaluated. One component of the PFT is the FEV1 value (the amount of air exhaled in one second). Physicians, families and patients keep track of the FEV1 values and decreases are investigated carefully and addressed with treatment modification, if necessary. Many industry-sponsored and CF Foundation-sponsored protocols use FEV1 values in their exclusion and inclusion criteria for studies involving patients with CF. FEV1 is used to judge the efficacy of most investigational treatments. (In many studies, change in FEV1 is the only primary endpoint measured.)

Almost all of our patients with CF participate in the national CF Foundation (CFF)-sponsored CF Registry. Detailed clinical information is collected through the Registry and published each year in the CFF Annual Data Report and online, from which some of the information is accessible to the public. The Data Report is meant to be one way to compare outcomes at different CF Centers. Also, it is used locally to identify areas that need further improvement. In the recently published 2008 Data Report, the average FEV1 values for patients at our Center ages 6-12 years had decreased significantly from last year. This continues a trend the investigators have seen over the past 5 years, despite no apparent change in the treatment protocols at our Center. Nationally, FEV1 values for patients in this age range have stayed the same. This apparent local decrease was quite troubling to our Center staff and became a recent focus of our Quality Improvement efforts.

Our Upstate CF Care Center is very active in research. For example, in 2009, 68 of our 135 pediatric patients have been participating in 16 clinical trials. Sponsors often provide their study sites with spirometers to use for PFTs. These machines are meant to provide uniform PFTs results for studies, which include measurement of FEV1 values. In 2009, among the 52 patients at our Center who are 6-12 years old, 20 (38%) have been in studies with sponsor-provided spirometers. Among the 32 patients ages 13-17 years, 13 (40%) have been in studies with sponsor-provided spirometers. Anecdotally, the investigators have noted that FEV1 results obtained during clinical trials for our patients appear to be lower than those of our patients' usual values, especially with younger children. The investigators hypothesize that the apparent difference in PFT results might be related to the different incentives (if any) provided by study PFT equipment. Further, if this difference exists, the investigators believe that this may account for the apparent average decline in the lung function results of our patients over the recent years, given the large proportion of our patients who participate in clinical trials. Finally, the investigators hypothesize that younger children may be more affected by the difference in incentives than older ones.

The purpose of this study is to collect an additional set of PFTs using our regular clinic equipment, on all study subjects following their study PFTs if these are done with sponsor-provided equipment. The investigators will compare the results from both types of machines and report regarding differences identified.