Diagnosis and Management of Cystic Fibrosis Exacerbations

Abstract

With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is acute pulmonary exacerbation (PEx). Clinical and microbial epidemiology studies of CF PEx continue to provide important insight into the disease course, prognosis, and complications. This work has now led to several large-scale clinical trials designed to clarify the treatment paradigm for CF PEx. The primary goal of this review is to provide a summary and update of the pathophysiology, clinical and microbial epidemiology, outcome and treatment of CF PEx, biomarkers for exacerbation, and the impact of highly effective modulator therapy on these events moving forward.

Figure 1.

FEV₁ for nonresponders and responders at baseline, treatment initiation, and the best FEV₁ in the 3 months after treatment (n = 4,391). Responders are in white, nonresponders are in gray. The boxes represent the middle 50% of patients; the whiskers include all patients in each group. The horizontal line within the box represents the median FEV₁. The x axis represents three time points: the best FEV₁ in the 6 months before admission (baseline); FEV₁ at treatment initiation (exacerbation); and the best FEV1 in the 3 months after treatment (follow-up). Reprinted with permission from the AJRCCM. * represent P<0.05

Figure 2a, 2b and 2c.

STOP2 study outcomes by Visit, allocation and antimicrobial treatment duration: A) primary outcome ppFEV1 B) Chronic Respiratory Infection Symptom Score (CRISS), C) weight. V1=Visit 1at start of IV antimicrobials; V2=Visit 2 when randomization occurs, V3=Visit 3 was targeted for 14 days after scheduled end of IV antimicrobial treatment. Treatment arms are the Early Robust Responders (ERR) and Non-Early Robust Responders (NERR). Treatment response was assessed at day 7-10 of IV antibiotic treatment and the cut point to determine ERR was ≥ 8% improvement in FEV1 and ≥ 11 points on the CRISS. Reprinted with permission from the AJRCCM.

Figure 3.

IV Antibiotic Treatment Durations(hospitalized and not hospitalized) in the US CFFPR. Distribution of IV antibiotic treatment durations. Black bars show numbers of patients of a given treatment duration who were never admitted to hospital as part of their exacerbation treatment. Reprinted with permission of the Journal of Cystic Fibrosis.