COPD, 00:1–10, 2014 ISSN: 1541-2555 print / 1541-2563 online Copyright © Informa Healthcare USA, Inc. DOI: 10.3109/15412555.2014.922174

ORIGINAL RESEARCH

COPD-related Bronchiectasis; Independent Impact on Disease Course and Outcomes

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Timothy Gatheral,1 Neelam Kumar,1 Ben Sansom,1 Dilys Lai,2 Arjun Nair,3 Ioannis Vlahos,3 and Emma H. Baker1 1

Institute of Infection and Immunity, St George’s, University of London, UK

2

Respiratory Medicine, Chelsea and Westminster Hospital, London, UK

3

Department of Radiology, St George’s Healthcare NHS Trust, London, United Kingdom

Abstract Background: COPD and radiographic bronchiectasis frequently coexist but the effect of this on the clinical course of COPD is not fully understood. We determined the impact of bronchiectasis on clinical outcomes in COPD patients, independent of coexisting emphysema and bronchial wall thickening (BWT). Methods: COPD patients admitted with first exacerbation 1998–2008 were identified retrospectively using ICD10 codes J44.0,1,8,9. Patients with suitable CT scans were graded for severity of bronchiectasis, emphysema and BWT on a 5 point scale (0-absent, 1-minor, 2-mild, 3-moderate, 4-severe). Results: 406 patients (71 ± 11 years, 56% male, FEV1 52 ± 23% predicted) were included; 278 (69%) patients had bronchiectasis: minor, 112 (40%); mild, 81 (29%); moderate, 62 (22%); severe 23 (8%). Bronchiectasis severity correlated with severity of BWT (p < 0.001) but not emphysema (p = 0.090). Bronchiectasis independently determined sputum isolation of Pseudomonas aeruginosa (Odds ratio (OR) 1.39 (95% CI 1.07 to 1.80), p = 0.013) and atypical mycobacteria (OR 2.44 (95% CI 1.04 to 5.69), p = 0.040), annual respiratory admissions (p = 0.044) and inpatient days (p < 0.001), but did not predict survival (p = 0.256). Conclusions: Radiographic bronchiectasis in COPD patients is associated with increased respiratory infection and hospitalisation, independent of coexisting emphysema and BWT. COPD-related bronchiectasis is therefore an important diagnosis with potential implications for treatment.

Introduction

Keywords: Airway, infection, computerised tomography, emphysema Correspondence to: Professor Emma H. Baker, Mailpoint J1A, Ist Floor Jenner Wing, Institute of Infection and Immunity, St George’s, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom, phone: +4420 8725 5383 or +447714 216417, email: [email protected].

Bronchiectasis is defined as “symptoms of persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi” (1). People with chronic obstructive pulmonary disease (COPD) commonly have “irreversibly damaged and dilated bronchi,” but it is unclear whether this relates to “persistent or recurrent bronchial sepsis,” independent of other pathological manifestations of this condition. Several studies utilising thoracic computed tomography (CT) scanning reveal a high prevalence of bronchiectasis in COPD patients, ranging from 20–58% in both primary and secondary care (2–4). By contrast, only 4% of COPD patients in ECLIPSE, a prospective biomarker evaluation study, had radiographic bronchiectasis (5). There is evidence that bronchiectasis influences clinical outcomes in COPD. Several small (44–118 patients) studies have shown that COPD patients with radiographic bronchiectasis are more likely than those without to: be chronic sputum producers (6, 7); have worse health status (7); have more airway (8) or systemic (6) inflammation and to have more purulent 1

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Gatheral et al.

sputum (3, 7). Potentially pathogenic microorganisms (PPM) were isolated more frequently from sputum of COPD patients with radiographic bronchiectasis during stability (6, 8), but in only one of two studies during exacerbation (4, 9). Martinez and colleagues found that COPD patients with radiographic bronchiectasis had more exacerbations and were more likely to have been hospitalized in the preceding year than those without (6). However, three other studies in stable outpatients (2, 7, 8) did not find that radiographic bronchiectasis was associated with increased rates of exacerbation prior to CT scanning. Taken together, these studies appear to indicate that radiographic evidence of “irreversibly damaged and dilated bronchi” is associated with “persistent or recurrent bronchial sepsis” in people with COPD. However, as the presence of bronchiectasis may also be related to the severity of airflow obstruction (5, 6), the effect of bronchiectasis on the clinical phenotype of COPD, independent of other pathologies such as emphysema and bronchial wall thickening, remains unclear. Parr and colleagues found that severity of airways disease had an independent effect on health status after adjustment for severity of emphysema (7). By contrast, Badafhel and colleagues found that radiographic bronchiectasis and/ or bronchial wall thickening did not have an independent effect on airway inflammation or bacterial load over and above the effect of emphysema (2). There are important differences between the management of non-cystic fibrosis (CF) bronchiectasis and COPD, suggesting that targeted management may be appropriate in patients where they co-exist. Accordingly, the aim of our study was to determine the clinical significance of radiographic bronchiectasis, independent of coexisting emphysema and bronchial wall thickening, in a 10-year cohort of COPD patients.

Methods Patients Patients were identified retrospectively at first hospital admission for COPD exacerbation using International Classification of Diseases (ICD10) codes J44.0/1/8/9. Patients were included in the study if they were admitted for first exacerbation between January 1998 and September 2008, had undergone CT scanning, and images were available for analysis. The National Research Ethics Committee approved the study (12/LO/0558), and judged that retrospective written informed consent from participants was not required. Radiology Thoracic CT scans were performed for a variety of clinical indications including investigation of dyspnoea, abnormal chest x-ray or to look for pulmonary embolus. The type of CT scanners and image reconstructions available at our institution varied during the study period. As such, CT scans were performed using either

a single section helical CT scanner, or 4-, 64- or 128-section multidetector CT scanners (GE Systems, Milwaukee, WI, USA, or Siemens Medical Systems, Forchheim, Germany). All imaging was acquired with or without intravenous contrast media using the following parameters: 120 kVp, mAs 160–310 mAs, 0.5 second rotation time, from apex to diaphragm in the supine position at maximal inspiration. Imaging was performed as either high resolution CT (HRCT) or non-HRCT thoracic imaging. HRCT was performed as either: prospective non-contiguous sequential scanning with 1mm collimation at 10mm increments (single section and 4 section CT); or as retrospective HRCT reconstructions using isotropic data sets from volumetric helical scanning (64–128 section CT). The 1 mm HRCT images were reconstructed at 28 to 32 cm field of view and a fixed matrix size of 512 × 512, using a high spatial frequency algorithm. NonHRCT thoracic imaging was performed as volumetric helical scanning with either 2.5 to 5 mm (4 to 128 section CT) or 7 mm (single section CT) collimation, with images also reconstructed using a high spatial frequency algorithm. For each patient, if there was a choice of thoracic CT scan available, the highest resolution scan was selected i.e., HRCT images with 1mm slices if available, or a scan with highest image quality if alternative scans had suffered movement degradation. All images were viewed at a window width and level of 1,600 and −500 Hounsfield units respectively. Semi-quantitative image analysis was performed by 2 specialist thoracic radiologists with extensive clinical experience in the field. Each scan was visually graded by consensus for emphysema, bronchial wall thickening and bronchiectasis using the following system:

Emphysema 0. Absent 1. Patchy foci of centrilobular or paraseptal emphysema in less than four segments 2. Foci of emphysema in four or more segments, but confined to an upper or upper/mid zone predominance, including asymmetrical bullous emphysema if lower lobes were spared 3. Emphysema which affects all lobes, but is not yet confluent or does not yet demonstrate marked diffuse bullous changes 4. Diffuse advanced confluent emphysema or with multilobar extensive bullous change.

Bronchial wall thickening 0. Absent 1. Minimal or equivocal, confined to subsegmental airways in three or less segments 2. Mild, in more than three segments, estimated wall thickness about 1 mm 3. Moderate, involving the majority of lobes, estimated wall thickness 2 mm Copyright © 2014 Informa Healthcare USA, Inc

COPD-related bronchiectasis

4. Severe, estimated wall thickness about 3mm or greater with mucoid impaction

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Bronchiectasis 0. Absent 1. Minimal, slightly dilated airways involving less than four segments, with dilatation and non-tapering of the airway OR Equivocal, where dilated airways were suspected, but confirmatory thin (i.e. HRCT) sections were unavailable 2. Mild, focal dilated airways that were only slightly enlarged, in 4–6 segments 3. Moderate, multiple foci of mildly-dilated airways OR a few foci of moderately-dilated airways 4. Severe. Diffuse airway dilatation throughout most lobes, of moderate-to-severe quality, with other features such as cystic or varicose bronchiectasis. Bronchiectasis was defined according to accepted criteria when one or more of the following were fulfilled: (1) an internal diameter of the bronchus greater than that of the adjacent pulmonary artery, (2) a lack of tapering of the bronchial lumen toward the periphery, or (3) visualization of the bronchus within 10 mm of the pleural space (10).

Clinical variables and outcomes Electronic patient records were used to retrieve demographic and clinical information. Participants were stratified according to severity of airflow limitation using the Global Initiative for Obstructive Lung Disease (GOLD) score (11). All available sputum microbiology reports were retrieved for each patient. Individual organisms isolated at any time, total number of different organisms isolated and persistent infection (same organism isolated in at least 2 months of a single year) were recorded. Charlson Index, a severity-weighted co-morbidity score, was derived from ICD10 codes for primary and other diagnoses at first admission (12). All subsequent admissions for each patient were retrieved and coded by primary diagnosis as being for respiratory (ICD codes J00-99) or non-respiratory (all other codes) causes. Admissions were expressed as number of admissions or inpatient days per patient per year of follow up. Deaths were identified from electronic records, updated weekly from national primary and secondary care records. Time from hospital admission was calculated as time to death or study end if patients survived. Analysis Continuous variables are given as mean ± standard deviation or median (interquartile range). Comparisons between groups were made for normally distributed data using one way analysis of variance (ANOVA) and for non-normally distributed data using Kruskal–Wallis www.copdjournal.com

tests. Categorical variables are given as number (percentage). Comparisons between categorical groups were made using Chi-square analysis. Univariate analysis determined independent relationships between increasing severity bronchiectasis and continuous clinical variables or outcomes, after adjustment for severity of emphysema and bronchial wall thickening. Logistic regression determined independent relationships between increasing severity bronchiectasis and binary clinical variables or outcomes, after adjustment for severity of emphysema and bronchial wall thickening. Odds ratio (OR) and 95% confidence intervals were used to describe effect size after adjustment for other variables in the model. Kaplan–Meier analysis was used to determine the effects of increasing severity bronchiectasis on survival from first admission. Survival was compared between patients with different severity bronchiectasis using the log rank test. Cox regression was used to determine the effect of increasing severity bronchiectasis on survival from first admission after adjustment for increasing severity emphysema and bronchial wall thickening, age at study entry, gender and Charlson index. All analyses were performed using PASW statistics version 21. P values

COPD-related bronchiectasis; independent impact on disease course and outcomes.

COPD and radiographic bronchiectasis frequently coexist but the effect of this on the clinical course of COPD is not fully understood. We determined t...
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