Antibiotic duration and changes in FEV1 are not associated with time until next exacerbation in adult cystic fibrosis: a single center study

Julia C Espel,Hannah L Palac,Alexandria P Clarke,Manu Jain,Joanne F Cullina,Susanna A Mccolley,Michelle H Prickett

doi:10.1186/s12890-017-0503-6

Julia C Espel, Hannah L Palac + Show 5 more

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https://doi.org/10.1186/s12890-017-0503-6

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Abstract

BackgroundPulmonary exacerbations (PEx) are a major driver of morbidity and mortality in cystic fibrosis and reducing their frequency by extending the time between them is an important therapeutic goal. Although treatment decisions for exacerbations are often made based on dynamic changes in lung function, it is not clear if these changes truly impact future exacerbation risk. We analyzed adults with chronic Pseudomonas aeruginosa infection to determine whether changes in FEV1 or duration of intravenous antibiotic therapy were associated with time to the next pulmonary exacerbation.MethodsMedical records and Cystic Fibrosis Foundation Patient Registry data were examined retrospectively to assess whether various patient-specific demographic factors and exacerbation-specific characteristics were associated with time until next exacerbation using the Andersen-Gill model in order to control for previous exacerbation frequency history.ResultsWe examined 59 patients with 221 CF pulmonary exacerbations over a 3-year study period. Mean age was 28.2 years and mean baseline FEV1 was 62% predicted. In our univariable model, fall in FEV1 at onset of exacerbation (median absolute −3% predicted change), recovery of FEV1 with treatment (median absolute +3% predicted change) and duration of IV antibiotics (median 16 days) were not associated with time to next exacerbation (median 93.5 days). Paradoxically each one-year increase in age was associated with a reduction in hazard of PEx by 3% (HR 0.97, P = 0.03, 95% CI 0.95–1.00).ConclusionsFEV1 drop and recovery associated with onset and treatment of a CF pulmonary exacerbation or duration of intravenous antibiotics were not predictive of time until next exacerbation. Our finding that older age may be associated with decreased hazard of exacerbation is likely due to a healthy survivor effect and should be controlled for in clinical trials of pulmonary exacerbations.

Highlights

Pulmonary exacerbations (PEx) are a major driver of morbidity and mortality in cystic fibrosis and reducing their frequency by extending the time between them is an important therapeutic goal
In concordance with the Cystic Fibrosis Foundation (CFF) guidelines [20], treatment for a PEx consisted of two intravenous antibiotics targeting P. aeruginosa, augmentation of chest physiotherapy, and continuation of all background therapies including inhaled antibiotics
Demographic data We examined 59 unique patients who experienced a total of 221 CF pulmonary exacerbations requiring IV antibiotics which calculates to 3.8(sd = 3.3) exacerbations per patient over 3 year study period

Summary

Introduction

Pulmonary exacerbations (PEx) are a major driver of morbidity and mortality in cystic fibrosis and reducing their frequency by extending the time between them is an important therapeutic goal. Bronchiectasis can occur early in life and develops from a cycle of airway infection, inflammation and mucus obstruction. Punctuating this chronic progressive process is the periodic development of CF pulmonary exacerbations. Pulmonary exacerbations (PEx) induce significant morbidity in patients, including more rapid lung function decline [3,4,5], failure to recover to previous FEV1 baseline [6], a loss in quality of life [7, 8], and an increased risk of death and lung transplantation [4]. PEx are generally managed by increasing the intensity of airway clearance treatments, oral or intravenous antibiotics, and other supportive measures [12, 13]

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