Standardized Treatment of Pulmonary Exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary Exacerbations

Abstract

Background: Pulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx.

Methods: The Standardized Treatment of Pulmonary Exacerbations (STOP) observational study enrolled 220 participants ≥12years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals.

Results: The mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (<50% FEV₁) were treated nearly two days longer than those with >50% FEV₁. Physician-reported FEV₁ improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV₁ ≤50% predicted compared with those with 6-month baseline FEV₁ >50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28days after the start of treatment. The mean absolute increase in FEV₁ from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV₁ was only recovered in 39% of PEx.

Conclusions: In this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful.

Keywords: Antibiotic therapy; Cystic fibrosis; Physician treatment practices; Pulmonary Exacerbations.

Figure 1.

Absolute changes from the best FEV₁ % predicted in the 6 months prior to admission compared to admission, day 7, end of IV antibiotic treatment, and day 28 FEV₁ % predicted. Black lines represent the individuals whose treatment goal was lung function recovery, and gray line represents the individuals whose treatment goal was improvement in signs and symptoms. Time intervals between visits vary by subject (as noted by double hashes), as end of IV antibiotic treatment varied by subject.

Figure 2.

Percentage of STOP patients who recovered the specified proportion of their baseline lung function (defined as prior 6-month best FEV₁) at day 28. For example, only 67% of individuals recovered 90% of their baseline lung function.

Figure 3.

CRISS and FEV₁ response from admission to day 28 in patients whose admission FEV₁ was < 6 month best FEV₁ compared to patients whose admission FEV₁ was > 6 month best FEV₁.

Figure 4.

Among participants with lung function recovery as the primary goal listed, this figure compares absolute difference in FEV1 % predicted from Day 28 spirometry measurement to the best measurement in the 12 months prior and 6 months prior, admission, and target FEV1. The groups are separated by treatment outcome (success vs non-success).

Figure 5.

Change in CRISS and FEV₁ from admission to day 28 in patients with all data available compared to available and imputed data combined. Missing data was computed using the Last Observation Carried Forward (LOCF) method.