(139) Discovering Symptom Clustering Patters During a Pulmonary Exacerbation in People with Cystic Fibrosis

Background: Pulmonary exacerbations (PExs) in people with cystic fibrosis (CF) are characterized by a worsening in symptoms, and more research is needed to understand how symptoms group together during a PEx. A symptom cluster is when two or more symptoms co-occur and are related. Symptom clusters in chronic obstructive pulmonary disorder are associated with health care utilization and increased mortality. Symptom clusters have not been systematically studied in CF. The purpose of this study was to identify distinct symptom clustering patterns during a CF PEx.

Methods: This study (N=120) was a secondary, longitudinal analysis. Pediatric and adult participants were enrolled from 6 CF Foundation accredited centers across the Unites States, at least 10 years of age, and being treated with intravenous (IV) antibiotics for a CF PEx. The CF Respiratory Symptom Diary, a valid and reliable tool, measured eight symptoms (scored 0-4) and symptom burden (scored 0-24), where higher scores indicated worse symptoms. Symptoms were collected on treatment Days 1, 7, 14 and 21. K-means clustering was computed in R Studio to detect clustering patterns; t-test, Wilcoxon rank-sum test and chi-square tests were used to test differences between discovered groups.

Results: Symptoms significantly clustered based on severity on Days 1 (n=72) and 7 (n=79) of a PEx. On Day 1, Cluster 1 (n=42) was low symptom severity, symptom burden mean 6.60 (SD 2.9), and Cluster 2 (n=30) was high symptom severity, symptom burden mean 14.3 (SD 2.7); figure 1 depicts a visual representation Day 1 clusters. Cluster 2 had significantly higher symptom scores on seven of the eight symptoms than Cluster 1, except the symptom assessing fevers (p=0.29). There was a significant difference between age and days spent in the hospital: Cluster 1 mean age was 21.02 and days spent 23.9, Cluster 2 mean age was 26.7 and days spent 41.6.There was no difference between Cluster 1 and 2 on Day 1 ppFEV1, race, gender, P. aeruginosa infection, type of insurance, nutrition, or smoke exposure. On Day 7, symptoms continued to cluster based on severity. Cluster 1 (n=60) was low symptom severity, symptom burden mean 2.65 (SD 1.72), and Cluster 2 (n=19) was high symptom severity, symptom burden mean 8.68 (SD 3.3). Six of the eight symptoms continued to be significantly different between Clusters 1 and 2, except feverish and chill/sweats. Most symptoms significantly improved between Day 1 and 7 Cluster 1, and Day 1 and 7 Cluster 2.

Conclusions: Symptoms significantly cluster based on severity on Days 1 and 7 of a PEx in people with CF. There was not a significant difference in lung function between Day 1 Cluster 1 and Cluster 2, suggesting that higher symptom burden is not associated with worsening lung disease severity. On Day 1, participants who grouped into Cluster 2 spent significantly more days in the hospital than Cluster 1, suggesting that people with higher symptom burden may be at higher risk for spending more days in the hospital. Further, the findings that symptoms significantly improve between Day 1 and Day 7 clusters suggest that symptoms are sensitive to PEx IV antibiotic therapy.

Acknowledgements: This work was supported by the National Institutes of Health [T32NR019035] and the Cystic Fibrosis Foundation [GILL21H0].

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