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, Joanne F. Cullina, Alexandria P. Clarke, Susanna A. McColley, Michelle H. Prickett, Manu Jain*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: 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. 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. Methods: Medical 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. Results: We examined 59 patients with 221 CF pulmonary exacerbations over a 3-year study period. Mean age was 28.2years 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 16days) were not associated with time to next exacerbation (median 93.5days). 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). Conclusions: FEV1 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.

Original languageEnglish (US)
Article number160
JournalBMC Pulmonary Medicine
Volume17
Issue number1
DOIs
StatePublished - Nov 29 2017

Fingerprint

Cystic Fibrosis
Anti-Bacterial Agents
Lung
Therapeutics
Pseudomonas Infections
Controlled Clinical Trials
Pseudomonas aeruginosa
Medical Records
Survivors
Registries
History
Demography
Morbidity
Mortality

Keywords

  • Antibiotics
  • Bronchiectasis
  • Cystic fibrosis
  • Exacerbation
  • Outcomes Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

@article{a06fe5aaaf3e470baed9aa8c167d1049,
title = "Antibiotic duration and changes in FEV1 are not associated with time until next exacerbation in adult cystic fibrosis: A single center study",
abstract = "Background: 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. 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. Methods: Medical 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. Results: We examined 59 patients with 221 CF pulmonary exacerbations over a 3-year study period. Mean age was 28.2years 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 16days) were not associated with time to next exacerbation (median 93.5days). 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). Conclusions: FEV1 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.",
keywords = "Antibiotics, Bronchiectasis, Cystic fibrosis, Exacerbation, Outcomes Pseudomonas aeruginosa",
author = "Espel, {Julia C.} and Palac, {Hannah L.} and Cullina, {Joanne F.} and Clarke, {Alexandria P.} and McColley, {Susanna A.} and Prickett, {Michelle H.} and Manu Jain",
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month = "11",
day = "29",
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language = "English (US)",
volume = "17",
journal = "BMC Pulmonary Medicine",
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Antibiotic duration and changes in FEV1 are not associated with time until next exacerbation in adult cystic fibrosis : A single center study. / Espel, Julia C.; Palac, Hannah L.; Cullina, Joanne F.; Clarke, Alexandria P.; McColley, Susanna A.; Prickett, Michelle H.; Jain, Manu.

In: BMC Pulmonary Medicine, Vol. 17, No. 1, 160, 29.11.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antibiotic duration and changes in FEV1 are not associated with time until next exacerbation in adult cystic fibrosis

T2 - A single center study

AU - Espel, Julia C.

AU - Palac, Hannah L.

AU - Cullina, Joanne F.

AU - Clarke, Alexandria P.

AU - McColley, Susanna A.

AU - Prickett, Michelle H.

AU - Jain, Manu

PY - 2017/11/29

Y1 - 2017/11/29

N2 - Background: 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. 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. Methods: Medical 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. Results: We examined 59 patients with 221 CF pulmonary exacerbations over a 3-year study period. Mean age was 28.2years 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 16days) were not associated with time to next exacerbation (median 93.5days). 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). Conclusions: FEV1 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.

AB - Background: 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. 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. Methods: Medical 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. Results: We examined 59 patients with 221 CF pulmonary exacerbations over a 3-year study period. Mean age was 28.2years 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 16days) were not associated with time to next exacerbation (median 93.5days). 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). Conclusions: FEV1 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.

KW - Antibiotics

KW - Bronchiectasis

KW - Cystic fibrosis

KW - Exacerbation

KW - Outcomes Pseudomonas aeruginosa

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