Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis

Oriol Sibila, Elena Laserna, Amelia Shoemark, Holly R. Keir, Simon Finch, Ana Rodrigo-Troyano, Lidia Perea, Mike Lonergan, Pieter C. Goeminne, James D. Chalmers (Lead / Corresponding author)

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<10 5 cfu/g), moderate (10 5-10 6 cfu/g), andhigh bacterial load (≥10 7 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume200
Issue number1
Early online date21 May 2019
DOIs
Publication statusPublished - 1 Jul 2019

Fingerprint

Bronchiectasis
Bacterial Load
Anti-Bacterial Agents
Aztreonam
Quality of Life
Inflammation
Sputum
Therapeutics
Biomarkers
Prospective Studies
Confidence Intervals

Keywords

  • Airway inflammation
  • Inhaled aztreonam
  • QoL-B
  • Quality of life

Cite this

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title = "Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis",
abstract = "Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<10 5 cfu/g), moderate (10 5-10 6 cfu/g), andhigh bacterial load (≥10 7 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95{\%} confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63{\%} vs. 37{\%}; P = 0.01) and at Week 12 (62{\%} vs. 38{\%}; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.",
keywords = "Airway inflammation, Inhaled aztreonam, QoL-B, Quality of life",
author = "Oriol Sibila and Elena Laserna and Amelia Shoemark and Keir, {Holly R.} and Simon Finch and Ana Rodrigo-Troyano and Lidia Perea and Mike Lonergan and Goeminne, {Pieter C.} and Chalmers, {James D.}",
note = "Analysis of the AIR-BX studies was funded by Gilead Sciences inc. This study was funded by the European Respiratory Society through the EMBARC2 consortium and a short term research Fellowship to OS (STRTF201710-00217). OS is supported by PERIS 2017. JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research.",
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Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis. / Sibila, Oriol; Laserna, Elena; Shoemark, Amelia; Keir, Holly R.; Finch, Simon; Rodrigo-Troyano, Ana; Perea, Lidia; Lonergan, Mike; Goeminne, Pieter C.; Chalmers, James D. (Lead / Corresponding author).

In: American Journal of Respiratory and Critical Care Medicine, Vol. 200, No. 1, 01.07.2019, p. 33-41.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis

AU - Sibila, Oriol

AU - Laserna, Elena

AU - Shoemark, Amelia

AU - Keir, Holly R.

AU - Finch, Simon

AU - Rodrigo-Troyano, Ana

AU - Perea, Lidia

AU - Lonergan, Mike

AU - Goeminne, Pieter C.

AU - Chalmers, James D.

N1 - Analysis of the AIR-BX studies was funded by Gilead Sciences inc. This study was funded by the European Respiratory Society through the EMBARC2 consortium and a short term research Fellowship to OS (STRTF201710-00217). OS is supported by PERIS 2017. JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research.

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N2 - Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<10 5 cfu/g), moderate (10 5-10 6 cfu/g), andhigh bacterial load (≥10 7 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

AB - Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<10 5 cfu/g), moderate (10 5-10 6 cfu/g), andhigh bacterial load (≥10 7 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

KW - Airway inflammation

KW - Inhaled aztreonam

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