Predicting Pediatric CF Events with Patient-Reported Outcomes and Lung Measures

Mother helps her little boy to makes inhalation at home
Can acute respiratory events in children with cystic fibrosis be predicted using PRO tools that measure patient- and parent-reported respiratory symptoms?

In children with cystic fibrosis (CF), the combined use of patient- and parent-reported symptom information and objective lung function measures may help clinicians predict and manage acute respiratory events, according to study findings published in Journal of Cystic Fibrosis.

Recognizing that patient-reported outcomes (PROs) are important outcome measures in clinical practice and in research, investigators sought to assess the longitudinal variability of 2 measures of PROs — the Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory score and the Chronic Respiratory Infection Symptom Score (CRISS). Additionally, the researchers evaluated how well these PRO-based tools identified acute respiratory events among children with CF.

A secondary analysis of a prospective, observational study of school-aged children with CF was conducted at the Hospital for Sick Children in Toronto, Canada. Follow-up visits were completed by 98 participants every 3 months over a 2-year period (864 total visits). The parent-proxy (6 to 13 years of age) and self-reported (6 to 18 years of age) CFQ-R Respiratory score, and the CRISS (6 to 18 years of age), were measured at follow-up visits. Lung Clearance Index (LCI) and forced expiratory volume in 1 second (FEV1) were assessed as well.

Using the minimal important difference (MID) of each PRO as the threshold, the researchers compared the diagnostic accuracy of the PROs in differentiating acute respiratory events from clinically stable visits. Overall, the parent-proxy and the self-reported CFQ-R Respiratory scores were captured at 650 visits from 83 participants. Of these 650 visits, 427 were considered clinically stable, whereas 223 were deemed acute respiratory events. Additionally, the self-reported CFQ-R Respiratory score and CRISS were captured at 788 visits among the 98 participants, with 511 considered clinically stable and 277 deemed acute respiratory events.

Using data from stable visits at which both the parent-proxy and the self-reported CFQ-R Respiratory scores were completed (n=427), the investigators found that the mean parent score (89.6 points; 95% CI, 88.0-91.1) was significantly higher — that is, better — when compared with the self-reported score (84.9 points; 95% CI, 83.1-86.7; P <.001). In total, 25.1% and 19.4% of stable visits had a maximum score of 100 points (which represents no respiratory symptoms) for the parent-proxy and the self-reported CFQ-R Respiratory scores, respectively.

The positive predictive value (PPV) and negative predictive value (NPV) of a ≥8.5-point worsening in the parent-proxy CFQ-R score to identify acute respiratory events (n=119; PPV, 70.2%; NPV 87.0%) were higher than with the self-reported CFQ-R score (PPV, 58.9%; NPV, 72.2%). Further, the PPV and NPV of a ≥11-point change in CRISS for acute respiratory events (n=137) were 56.5% and 79.6%, respectively. When combined with the LCI and/or FEV1pp, the PPV and the NPV of all PROs were increased.

Several limitations of the current analysis warrant mention. Because no standardized definition of a pulmonary exacerbation is used in clinical practice, acute respiratory events were categorized according to reported changes in respiratory symptoms relative to baseline. Further, the MID of the parent CFQ-R Respiratory score might differ from the self-reported version of the score, which could potentially impact interpretation of the study results.

The investigators concluded that “The negative predictive value of the parent-proxy CFQ-R Respiratory score is high and, therefore, could be used rule out an acute respiratory event,” and that “the [positive predictive value] of the parent-proxy CFQ-R is increased by the addition of LCI as well as FEV1 [percent predicted].”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Perrem L, Stanojevic S, Shaw M, et al. Comparative analysis of respiratory symptom scores to detect acute respiratory events in children with cystic fibrosis. J Cyst Fibros. Published online June 23, 2022. doi:10.1016/j.jcf.2022.06.007