Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency

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Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency. / Stone, Helen; McNab, Gillian; Turner, Alice; Stockley, Robert A; Sapey, Elizabeth.

In: The European respiratory journal, Vol. 40, No. 3, 09.2012, p. 561-9.

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@article{2433386a571e4207813e38b77bd07c48,
title = "Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency",
abstract = "There is inherent daily variability of sputum inflammatory mediators in stable-state patients with usual chronic obstructive pulmonary disease (COPD). The variability of pulmonary inflammation in patients with α(1)-antitrypsin deficiency (A1ATD) is unknown. Our study aimed to quantify this variability, in comparison to patients with usual COPD, in order to facilitate power calculations for proof of concept trials of putative specific anti-inflammatory agents in both groups. Sputum interleukin (IL)-8, myeloperoxidase (MPO), leukotriene B(4) (LTB(4)) and differential cell counts were measured in 12 usual COPD patients and 12 A1ATD patients on nine occasions over a 1-month period. All samples were obtained in the stable clinical state. There was significant daily variability in all mediators in all patients. A1ATD patients had higher sputum concentrations of IL-8 and LTB(4) compared with usual COPD, but lower levels of MPO and absolute neutrophil counts. Patients with usual COPD had more intra-patient variability, A1ATD patients demonstrated greater inter-patient variability. There are increased concentrations of pulmonary inflammatory mediators but fewer sputum neutrophils in A1ATD compared with usual COPD. The daily variability of inflammatory mediators and cell counts was significantly reduced in both groups by averaging sequential samples. This can be utilised to perform power calculations for future proof of concept studies; averaging three sequential samples appears optimum.",
keywords = "Adult, Aged, Cell Count, Female, Humans, Inflammation Mediators, Interleukin-8, Leukotriene B4, Male, Middle Aged, Peroxidase, Pulmonary Disease, Chronic Obstructive, Sputum, alpha 1-Antitrypsin Deficiency",
author = "Helen Stone and Gillian McNab and Alice Turner and Stockley, {Robert A} and Elizabeth Sapey",
note = "Publication in name of Alice Wood, which was the maiden name of Alice Turner",
year = "2012",
month = sep,
doi = "10.1183/09031936.00162811",
language = "English",
volume = "40",
pages = "561--9",
journal = "The European respiratory journal",
issn = "0903-1936",
publisher = "European Respiratory Society",
number = "3",

}

RIS

TY - JOUR

T1 - Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency

AU - Stone, Helen

AU - McNab, Gillian

AU - Turner, Alice

AU - Stockley, Robert A

AU - Sapey, Elizabeth

N1 - Publication in name of Alice Wood, which was the maiden name of Alice Turner

PY - 2012/9

Y1 - 2012/9

N2 - There is inherent daily variability of sputum inflammatory mediators in stable-state patients with usual chronic obstructive pulmonary disease (COPD). The variability of pulmonary inflammation in patients with α(1)-antitrypsin deficiency (A1ATD) is unknown. Our study aimed to quantify this variability, in comparison to patients with usual COPD, in order to facilitate power calculations for proof of concept trials of putative specific anti-inflammatory agents in both groups. Sputum interleukin (IL)-8, myeloperoxidase (MPO), leukotriene B(4) (LTB(4)) and differential cell counts were measured in 12 usual COPD patients and 12 A1ATD patients on nine occasions over a 1-month period. All samples were obtained in the stable clinical state. There was significant daily variability in all mediators in all patients. A1ATD patients had higher sputum concentrations of IL-8 and LTB(4) compared with usual COPD, but lower levels of MPO and absolute neutrophil counts. Patients with usual COPD had more intra-patient variability, A1ATD patients demonstrated greater inter-patient variability. There are increased concentrations of pulmonary inflammatory mediators but fewer sputum neutrophils in A1ATD compared with usual COPD. The daily variability of inflammatory mediators and cell counts was significantly reduced in both groups by averaging sequential samples. This can be utilised to perform power calculations for future proof of concept studies; averaging three sequential samples appears optimum.

AB - There is inherent daily variability of sputum inflammatory mediators in stable-state patients with usual chronic obstructive pulmonary disease (COPD). The variability of pulmonary inflammation in patients with α(1)-antitrypsin deficiency (A1ATD) is unknown. Our study aimed to quantify this variability, in comparison to patients with usual COPD, in order to facilitate power calculations for proof of concept trials of putative specific anti-inflammatory agents in both groups. Sputum interleukin (IL)-8, myeloperoxidase (MPO), leukotriene B(4) (LTB(4)) and differential cell counts were measured in 12 usual COPD patients and 12 A1ATD patients on nine occasions over a 1-month period. All samples were obtained in the stable clinical state. There was significant daily variability in all mediators in all patients. A1ATD patients had higher sputum concentrations of IL-8 and LTB(4) compared with usual COPD, but lower levels of MPO and absolute neutrophil counts. Patients with usual COPD had more intra-patient variability, A1ATD patients demonstrated greater inter-patient variability. There are increased concentrations of pulmonary inflammatory mediators but fewer sputum neutrophils in A1ATD compared with usual COPD. The daily variability of inflammatory mediators and cell counts was significantly reduced in both groups by averaging sequential samples. This can be utilised to perform power calculations for future proof of concept studies; averaging three sequential samples appears optimum.

KW - Adult

KW - Aged

KW - Cell Count

KW - Female

KW - Humans

KW - Inflammation Mediators

KW - Interleukin-8

KW - Leukotriene B4

KW - Male

KW - Middle Aged

KW - Peroxidase

KW - Pulmonary Disease, Chronic Obstructive

KW - Sputum

KW - alpha 1-Antitrypsin Deficiency

U2 - 10.1183/09031936.00162811

DO - 10.1183/09031936.00162811

M3 - Article

C2 - 22700846

VL - 40

SP - 561

EP - 569

JO - The European respiratory journal

JF - The European respiratory journal

SN - 0903-1936

IS - 3

ER -