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CHEST Original ResearchOBSTRUCTIVE LUNG DISEASES

Original Research

Bronchiectasis and COPD share many characteris-tics, from both the physiopathologic1,2and clinical-

functional viewpoints.3,4The relationship between themcan be summarized in two observations. First, they areboth common conditions, especially in older patients5-7;

it is, therefore, unsurprising to see patients with simul-taneous COPD and bronchiectasis. Second, someauthors have observed an association between the two,

reporting the presence of bronchiectasis in up to 50%of patients with moderate to severe COPD8,9; thissuggests that there may be a causal relationship in

which COPD is a risk factor for bronchiectasis. This

Background:Previous studies have shown a high prevalence of bronchiectasis in patients withmoderate to severe COPD. However, the factors associated with bronchiectasis remain unknownin these patients. The objective of this study is to identify the factors associated with bronchiecta-sis in patients with moderate to severe COPD.

Methods:Consecutive patients with moderate (50% ,FEV170%) or severe (FEV150%) COPDwere included prospectively. All subjects filled out a clinical questionnaire, including informationabout exacerbations. Peripheral blood samples were obtained, and lung function tests were per-formed in all patients. Sputum samples were provided for monthly microbiologic analysis for6 months. All the tests were performed in a stable phase for at least 6 weeks. High-resolutionCT scans of the chest were used to diagnose bronchiectasis.

Results:Ninety-two patients, 51 with severe COPD, were included. Bronchiectasis was present in53 patients (57.6%). The variables independently associated with the presence of bronchiectasis

were severe airflow obstruction (OR, 3.87; 95% CI, 1.38-10.5;P5 .001), isolation of a potentiallypathogenic microorganism (PPM) (OR, 3.59; 95% CI, 1.3-9.9;P5 .014), and at least one hospitaladmission due to COPD exacerbations in the previous year (OR, 3.07; 95% CI, 1.07-8.77;

P5 .037).Conclusion: We found an elevated prevalence of bronchiectasis in patients with moderate tosevere COPD, and this was associated with severe airflow obstruction, isolation of a PPM fromsputum, and at least one hospital admission for exacerbations in the previous year.

CHEST 2011;

140(5):11301137

Abbreviations: CFU5colony-forming unit; HRCT5high-resolution CT; PPM5potentially pathogenic microorganism

Factors Associated With Bronchiectasis in

Patients With COPD

Miguel ngel Martnez-Garca, MD; Juan Jos Soler-Catalua, MD; Yolanda Donat Sanz, MD;Pablo Cataln Serra, MD; Marcos Agramunt Lerma, MD; Javier Ballestn Vicente, MD;and Miguel Perpi-Tordera, MD

Manuscript received July 10, 2010; revision accepted April 13,2011.

Affiliations:From the Pneumology Unit (Drs Martnez-Garca,Soler-Catalua, and Cataln Serra), the Service of Internal Medicine(Dr Donat Sanz), and the Radiology Department (Drs AgramuntLerma and Ballestn Vicente), Requena General Hospital; theService of Pneumology (Dr Perpi-Tordera), La Fe UniversityHospital; and CIBER de enfermedades respiratorias (Dr Martnez-Garca), Valencia, Spain.Funding/Support:This work was supported in part by a publicgrant from the Sociedad Valenciana de Neumologa.

Correspondence to: Miguel ngel Martnez-Garca, MD,Unidad de Neumologa, Hospital General de Requena, ParajeCasa Blanca s/n, 43230 Valencia, Spain. E-mail: [email protected] 2011 American College of Chest Physicians.Reproductionof this article is prohibited without written permission from theAmerican College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).DOI: 10.1378/chest.10-1758

For editorial comment see page 1107

hypothesis has yet to be demonstrated, but the mostrelevant information in the current literature showsthat patients with COPD and bronchiectasis have

wnloaded From: http://journal.publications.chestnet.org/ on 07/07/2013
mailto:[email protected]://www.chestpubs.org/site/misc/reprints.xhtmlhttp://www.chestpubs.org/site/misc/reprints.xhtmlhttp://www.chestpubs.org/site/misc/reprints.xhtmlmailto:[email protected]://www.chestpubs.org/site/misc/reprints.xhtmlhttp://www.chestpubs.org/site/misc/reprints.xhtml

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nary lobes and segments affected, with the lingula considered asan independent lobe. The HRCT scans were interpreted inde-pendently by two radiologists (M. A. L. and J. B. V.) with extensiveexperience in the diagnosis of bronchiectasis; both were blind tothe other researchers. Small bronchiectases only visible in a singlepulmonary segment were not considered, as these can appear in asignificant percentage of the healthy population, as previouslyreported.21

Interview Questionnaire, Lung Function, and Blood Samples

Data were collected from all the subjects during a medicalvisit marking their admission into the study using protocolizedmedical history questionnaires, both general and pulmonary.This information included general data (age and sex), smokinghabits (pack-years), clinical profile (presence and frequencyof chronic expectoration and Medical Research Council scale fordyspnea),22semiquantitative evaluation of the daily quantity ofsputum produced (,10 mL, 10-30 mL, or .30 mL), and ongoingtreatment. In addition, peripheral levels of fibrinogen (mg/dL),C-reactive protein (IU/mL), a1-antitrypsin (ng/dL), and albumin(mg/dL) were obtained as markers of systemic inflammation andnutritional status, respectively. Finally, data were collected fromarterial blood samples (Po2[mm Hg] and Pco2[mm Hg]) and

forced spirometry, in both absolute and percentage values overtheoretic values, both before and 15 min after bronchodilatortreatment with 200 g of inhaled salbutamol.

Exacerbation Variables

All the patients were instructed to visit their primary care phy-sician, outpatient urgent care, or hospital ED (depending on theseverity of their condition) whenever they noticed any symptomsof acute exacerbations; they were also asked to record detailedinformation about their condition and prescribed medication(courses of oral steroids and antibiotics). This information wasprovided by the patients themselves in follow-up outpatient visitsand subsequently confirmed by the hospitals clinical recordsand the computerized medical records shared with primary care

physician in the year prior to the HRCT scan. COPD exacerba-tion was defined as an increase in at least two out of three clinicalsymptoms (increase in dyspnea, sputum quantity, and sputumpurulence), or as the need for urgent care or hospitalization, oras the prescription of courses of antibiotics or steroids as a con-sequence of an increase in respiratory symptoms associated withCOPD.

Sputum Samples

A monthly microbiologic analysis of spontaneous morning spu-tum was requested from each patient in the 6 months subsequentto inclusion in the study (six sputum samples per patient). Patients

were taught the correct procedure for collecting monthly sputumsamples at home, using the most sterile technique possible, and

they were asked to deposit these samples in the hospital labora-tory, always within a maximum of 3 h after collection. Sputumsamples were accepted if they contained ,25 squamous epithe-lial cells per low-powered field and .25 leukocytes per high-powered field. The samples were separated from saliva, Gramstained, and homogenized. Diluted secretions were plated on blood,chocolate, and McConkey and Sabouraud agar. Sputum cultures

were expressed as colony-forming units (CFUs) per milliliter. For thepurposes of this study, a cutoff point of 103was defined as sig-nificant for the identification of abnormal positive culture resultsfor PPM, according to published methods.23-25Isolated bacterialagents were classified into PPM strains, such as Haemophilus

influenzae , Streptococcus pneumoniae, Moraxella catarrhalis,Haemophilus parainfluenzae, Staphylococcus aureus, Pseudomonas

greater bronchial inflammation, greater chronic colo-nization of bronchial mucosa by a potentially patho-genic microorganism (PPM), and a longer duration ofacute infectious exacerbations.8

If there is truth in the hypothesis that patientswith both COPD and bacterial colonization by PPMhave a worse prognosis,10-15the early identification ofpatients with COPD and severe bronchiectasis would

be a significant advance, as it would provide opportu-nities to start early treatment. It would be useful tounderstand the factors associated with bronchiectasisin patients with COPD on the basis of easily availabledata collected in routine medical visits. This wouldallow the clinician to select with a greater level ofconfidence those patients eligible for the relevantcomplementary tests (eg, high-resolution CT [HRCT]scan of the chest)16,17that would provide a definitivediagnosis. Therefore, the objective of this study wasto identify the factors associated with bronchiecta-sis, using routine data collected during medical visits

from patients diagnosed with moderate or severeCOPD.

Materials and Methods

Study Subjects

The study prospectively included 106 consecutive patientsdiagnosed with COPD, according to international standards,in our specialist outpatient clinic between January 2004 andDecember 2006. COPD was defined as a postbronchodilator ratioof FEV1/FVC,70%, adjusted for age and height in a patient with

a smoking habit of .10 pack-years and b2-agonist reversibility onpredicted FEV1of,15% and/or 200 mL. COPD was defined asmoderate if the postbronchodilator FEV1was70% and severeif the postbronchodilator FEV1was 50%.18The diagnosis ofCOPD was confirmed in all patients by a respected internationalCOPD expert who has run our COPD specialist outpatient clinicfor more than a decade. Special care was taken to rule out anypatients with a possible diagnosis of bronchiectasis prior to thatof COPD and any possible diagnostic errors, so all the necessarycomplementary tests were performed in this respect.

Patients with a prior diagnosis of bronchiectasis were excludedfrom the study, as were those whose deteriorated basal conditionprevented them from undergoing an HRCT scan (as reported bya radiologist). Patients were recruited in a stable phase, with noevidence of any exacerbations for at least 6 weeks, as defined else-

where.19All tests involved in the study were also performed in thisstable phase. All patients signed an informed consent agreementto participate in the study, which was approved by the EthicsCommittee of our hospital (Hospital General Universitario de

Valencia; approval number: 0089).

Diagnosis of Bronchiectasis

All the patients were diagnosed as having bronchiectasis aftera chest HRCT scan. High-resolution images were obtained infull inspiration at 1 mm collimation and 10-mm intervals from theapex to the base of the lungs. The presence of bronchiectasis wasbased on criteria published by Naidich et al.20The extent of thebronchiectasis was evaluated according to the number of pulmo-

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1132 Original Research

diseases, infection by nontuberculous microbacteria,or high-risk professions [85% were retired farm

workers], and so forth). An average of three validsputum samples was collected from each patientduring the 6 months of the study (range, zero to sixsamples). Table 1 shows the basic characteristics ofthe bronchiectasis found in the patients included inthe study.

Tables 2 and 3 show the differential characteris-tics of the groups with (n553) and without (n539)bronchiectasis. Patients with COPD and bronchiec-tasis presented more symptoms, particularly morechronic expectoration, more exacerbation indices,greater systemic inflammation (fibrinogen concen-tration), poorer nutritional status (albumin con-centration), more severe airflow obstruction, morepositive cultures of PPMs, and greater chronic PPMcolonization.

Table 4 describes the PPMs identified during thestudy. Thirty-nine patients (42.4%) had PPMs in at

least one sputum sample over the course of the study.Twenty patients (21.7%) presented chronic PPM

aeruginosa, Klebsiella pneumoniae, and other gram-negative rods.The presence of a single PPM in at least three different monthlysputum samples, without any concurrent antibiotic treatment,

was considered chronic colonization.26The bacterial colonizationtests were performed by technical staff blind to the clinical char-acteristics of the subjects in the study.

Statistical Analysis

The statistical package SPSS, version 15.0 (SPSS; Chicago,

Illinois), was used for the statistical analysis. All data were tabulatedas mean and SD in the case of quantitative variables and as abso-lute numbers and percentages in the case of qualitative variables.The Kolmogorov-Smirnov test was used to analyze the distribu-tion of variables. Patients were assigned to two groups, those withand without bronchiectasis. In the bivariate analysis, variables

with a normal distribution were analyzed using the Studentttestfor independent variables, or the Mann-Whitney Utest in othercases. Qualitative variables were compared with the x2test, usingthe Yates correction when necessary. As the objective of thestudy was to establish a predictive model for easy use, the vari-ables courses of antibiotics in previous year (at least four courses[x2, 6.06; P5 .01]), courses of oral corticoids in previous year(at least two treatments [x2, 3.45; P5 .04]), visits to emergency

room in previous year (at least two [x2

, 3.91; P5 .03]), andhospital admissions in previous year (at least one [x2, 4.75;P5 .024]) were dichotomized. The cutoff points for these variables

were established as those with the greatest capacity to discrimi-nate between patients with and without bronchiectasis (x2test).A logistic regression model was used to determine factors inde-pendently with respect to the presence of bronchiectasis. Those

variables that presented statistical ly significant differences inthe bivariate analysis, as well as being of clinical interest, wereincluded as the independent variables in the first step. In cases ofelevated collinearity between two variables (Spearman correlationtest.0.6), the variable with greater clinical significance was cho-sen, according to the authors judgment. The forward technique(Wald test) was used to remove variables with a P..1 from thelogistic model. ORs and 95% CIs were obtained for the indepen-

dent variables. Pvalues.05 were considered significant.

Results

One-hundred six patients with moderate to severeCOPD were analyzed. Eight were excluded fromthe study because of previous diagnoses of bron-chiectasis, four were unable to undergo HRCT scan,and two had uninterpretable HRCT scan results. Ofthe 92 patients remaining in the study (mean age71.3 [9.3] years; 99% men), 51 (55.4%) had severe

COPD and 41 (44.6%) had moderate COPD. Fifty-three patients (57.6%) presented bronchiectasis (72.5%of the subjects with severe COPD and 34.7% of thesubjects with moderate COPD; P5.01). Five patientshad a history of TB (5.4%), and 35 patients had a his-tory of at least one pneumonia (38%); of the latter,21 presented bronchiectasis. Pneumonia occurredsubsequent to the diagnosis of bronchiectasis in16 of these 21 patients. No other disease capable oftriggering bronchiectasis was found in our patients(eg, deficit ofa1-antitrypsin, allergic bronchopulmonaryaspergillosis, significant immunodeficiencies, systemic

Table 1Bronchiectasis Characteristics and OtherCT Scan Findings in Patients With COPD and

Bronchiectasis

Characteristics Absolute No. (%)

Patients with bronchiectasis 53 (57.6)Typea

Cylindric 48 (90.6) Cystic 10 (18.9)Location

Only upper lobes 6 (11.3) Only lower lobes 32 (60.4) Only lingula or middle lobule 15 (28.3) Only right 7 (13.2) Only left 5 (9.4) Bilateral 41 (77.4) Central bronchiectasis 2 (3.8)Extension Localized (only one lobule) 8 (15.1) Disseminated (four or more lobules) 10 (18.9) No. affected lobules, mean (SD) 2.1 (2.2) No. affected segments, mean (SD) 3.8 (4.6)Thickening of bronchial wallb

Slight 35 (66)

Moderate 15 (28.3) Severe 3 (5.7)Other findings Adenopathies (.10 mm) 16 (30.2) Atelectasis 15 (28.3) Radiologic signs of pulmonary hypertension 15 (28.3) Mucous plugs 15 (28.3) Bronchiolitis signs 14 (26.4) Chronic interstitial fibrosis 12 (22.6)

Data are presented as No. (%) unless otherwise noted.aSome patients had both cylindric and cystic bronchiectasis.bSlight thickening is less than the diameter of the adjacent vessel;moderate, similar to the diameter of the adjacent vessel; severe,greater than the diameter of the adjacent vessel.


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characteristics of the patient with moderate to severeCOPD.

Discussion

Based on our results, the presence of a severe airflowobstruction (FEV150%), a positive culture of a PPM

from a sputum sample, and at least one hospital admis-sion for acute exacerbation in the previous year arefactors independently associated with bronchiectasisin patients with moderate or severe COPD.

The prevalence of bronchiectasis in patients withmoderate to severe COPD in this study was 57.6%;it was primarily of a cylindric type, localized in thelower lobes, with a frequency distribution very simi-lar to that found by Patel et al8(50%) in moderate tosevere COPD. These findings confirm the presenceof an association between these disorders. In fact,it was those patients with both COPD and severe

colonization, and 24 patients (26.1%) presented PPMin single cultures (six presented two different PPMs).Nine patients with chronic PPM colonization alsohad positive cultures for a separate PPM during thestudy. The most frequently isolated microorganism wasH influenzae(46.2% of single positive cultures and50% of chronic PPM colonization). No samples couldbe collected from eight patients (8.7%).

Table 5 shows the results of the logistic regressionwith the final eight variables selected, each easilyobtained in clinical practice. Of these, the presenceof severe airflow obstruction (FEV150%; OR, 3.87;95% CI, 1.38-10.5; P5 .01), the isolation of a PPMin at least one sputum sample (OR, 3.59; 95% CI,1.3-9.9; P5 .014), and the need for at least one hospi-tal admission for acute exacerbation of COPD in theprevious year (OR, 3.07; 95% CI, 1.07-8.77; P5 .037)

were independently associated with bronchiecta-sis. Figure 1 shows an individual probability treefor the presence of bronchiectasis, depending on the

Table 2Baseline and Clinical Characteristics of Subjects With COPD, With and Without Bronchiectasis

Parameter Whole Group COPD With Bronchiectasis COPD Without Bronchiectasis PValue

Subjects, No. (%) 92 53 (57.6) 39 (42.4) Gender, male (female), No. 91 (1) 52 (1) 39 (0) nsAge, y 71.3 (9.3) 72.6 (8.7) 69.1 (9.7) nsPack-y smoked 65.9 (37.5) 69.8 (40.1) 60.6 (33.4) nsSmoking, No. (%) Current 19 (20.7) 12 (22.6) 7 (17.9) ns

Former 73 (79.3) 41 (77.4) 32 (82.1) nsOnset of symptoms, y 16.2 (15.4) 17.6 (15.4) 14.3 (15.3) nsDaily sputum production, No. (%) 48 (52.2) 34 (64.2) 14 (35.9) .007Sputum/d, No. (%) ,10 mL 44 (47.8) 19 (35.8) 25 (64.1) .01 10-30 mL 24 (26.1) 14 (26.4) 10 (25.6) .30 mL 24 (26.1) 20 (37.7) 4 (10.3)Usual sputum aspect,aNo. (%) Mucoid 79 (85.9) 46 (86.8) 33 (84.6) ns Mucopurulent 8 (8.7) 4 (7.5) 4 (10.3) Purulent 4 (4.3) 2 (3.8) 2 (5.1) Hemoptoic 1 (1.1) 1 (1.9) 0Daily treatments, No. (%) Anticholinergic 74 (80.4) 43 (81.1) 31 (79.5) ns LABA 22 (24) 13 (24.5) 9 (23.1) ns Combined treatment 57 (62) 32 (60.4) 25 (64.1) ns Home oxygen therapy 25 (27.1) 20 (37.7) 5 (12.8) .007Dyspnea MRC 1.86 (1.18) 2.04 (1.24) 1.63 (1.12) ns

Wheezing, No. (%) 46 (50) 30 (56.6) 16 (41) nsPrevious TB, No. (%) 5 (5.4) 5 (9.4) 0 nsPrevious pneumonia, No. (%) 35 (38) 21 (39.6) 14 (35.9) nsExacerbations, previous y PC visits 1.6 (2.2) 1.96 (2.9) 1.13 (1.7) .04 Outpatient UC visits 0.87 (1.55) 1.08 (1.78) 0.59 (1.1) .03 ED hospital visits 0.93 (1.3) 1.26 (1.47) 0.49 (0.99) .005 Hospital admissions 0.39 (0.8) 0.57 (0.95) 0.15 (0.36) .01Acute antibiotic treatments 1.85 (1.93) 2.34 (2.17) 1.18 (1.29) .004Acute oral steroid treatments 1.12 (1.5) 1.45 (0.67) 0.67 (1.13) .01

Data are presented as mean (SD) except as otherwise noted. LABA5long-acting b-agonist; MRC5Medical Research Council; ns5not significant;PC5primary care; UC5urgent care.aEight patients were unable to provide any sputum samples during the study.


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some patients with COPD. COPD could thereforebe a risk factor for bronchiectasis, although longitudi-nal studies are needed to demonstrate this hypothesis.The presence of P aeruginosa, in the form of either asingle isolate or chronic colonization, was not associated

with bronchiectasis in our study (as it has been in otherpublished research28), even though seven patients pre-sented positive cultures for this PPM (four as chroniccolonization), and six of these presented bronchiecta-sis. Although our results indicate that the presence of

P aeruginosacould potentially be a marker for bron-chiectasis in patients with moderate to severe COPD,the small number of subjects did not allow us to drawany conclusions on this point.

Finally, at least one hospital admission for acuteexacerbation of COPD in the year prior to inclu-sion in the studyconsidered a marker of severeexacerbationswas also independently associated

with bronchiectasis. The use of a cutoff point higher

functional impairment (FEV150%) who presenteda greater prevalence of bronchiectasis (.70%) in ourstudy, making this variable the best predictor ofbronchiectasis in the logistical model.

The second factor most associated with thepresence of bronchiectasis was positive culture of aPPM from at least one sputum sample (.103CFU/mL

yield in the culture). These results concur once againwith those reported by Patel et al,8who observed,in 54 patients with moderate to severe COPD, that

greater bronchial colonization by PPM was asso-ciated with the presence of bronchiectasis, with adistribution of microorganisms very similar to thatfound in our study. According to the hypotheses ofCole et al,27it is possible that the presence of PPMand concomitant proteolytic products is responsiblefor triggering the mechanism that generates bron-chiectasis, along with the chronic inflammation of thebronchial mucosa secondary to this phenomenon in

Table 3Analytic, Microbiologic, and Functional Characteristics of Subjects With COPD, With and WithoutBronchiectasis

Parameter Whole GroupCOPD With

BronchiectasisCOPD WithoutBronchiectasis PValue

Subjects, No. (%) 92 53 (57.6) 39 (42.4) Fibrinogen, mg/dL 397 (86.3) 417.2 (93.6) 367.9 (66.6) .008Albumin, mg/dL 4.21 (0.35) 4.14 (0.39) 4.31 (0.26) .025CRP, IU/mL 7.94 (12.2) 9.9 (15.5) 5.2 (4.09) ns

a1-Antitrypsin, ng/dL 162.1 (30.5) 166.3 (29.2) 156.1 (31.8) nsPo2/Pco2, mm Hg 63.4/42.9 61.9/43.4 65.4/42.3 nsFEV1/FVC, % predicted 47.6 (11.8) 45.1 (11,9) 51.2 (10.1) .02Post-BD FEV1, mL 1,210 (433) 1,107 (397) 1,350 (446) .007 % Predicted 49.9 (15.6) 46.4 (16,3) 54.8 (13.3) .01Post-BD FVC, mL 2,607 (753) 2,478 (659) 2,783 (841) ns % Predicted 80 (18.6) 77.3 (18.2) 83.7 (18.7) nsFEV150%, No. (%) 51 (55.4) 37 (69.8) 14 (35.9) .001Patients with at least one PPM isolate, No. (%)a 39 (42.4) 25 (47.2) 14 (35.9) .01Patients with chronic colonization by PPM, No. (%) 20 (21.7) 18 (33.9) 2 (5.1) .001Pseudomonas aeruginosaisolates, No. (%) 7 (7.6) 6 (11.3) 1 (2.6) nsHaemophilus influenzaeisolates, No. (%) 28 (30.4) 20 (37.7) 8 (20.5) ns

Data are presented as mean (SD) except as otherwise noted. BD 5bronchodilator; CRP5C-reactive protein; PPM5potentially pathologicmicroorganism. See Table 2 legend for expansion of the other abbreviation.a

Not including patients with chronic colonization.

Table 4PPMs Found During the Study

PPM

COPD With Bronchiectasis COPD Without Bronchiectasis

Isolationa(n525) Chronic Colonization (n518) Isolationa(n514) Chronic Colonization (n52)

Haemophilus influenzae 12 8 6 2Streptococcus pneumoniae 6 3 4 0Moraxella catarrhalis 4 2 3 0Pseudomonas aeruginosa 2 4 1 0Haemophilus parainfluenzae 0 1 0 0Klebsiella pneumoniae 1 0 0 0

Data from the 44 patients with single isolates of a PPM (left-hand column) or chronic colonization by PPMs (right-hand column). See Table 3legend for expansion of abbreviation.aEighteen patients with a single PPM isolate, plus six patients with two separate PPM isolates, plus nine patients with chronic PPM colonization andpositive cultures for a separate PPM during the study. Isolates that form part of a chronic colonization were not included (a chronic colonization

was defined as at least three isolates in three different months).


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nificant collinearity observed with other variables inthe model, such as the culture of a PPM from sputumor hospital admission in the previous year, and (2) theconsequent partial explanation of their predictive

power. It has been reported, in both COPD11

and bron-chiectasis,27that increased bronchial inflammationinduced by the presence of PPMs leads to increased

volume and greater frequency of expectoration.Among the limitations of our study is the use of a

semiquantitative measure (CFU/mL) for spontaneoussputum samples, with a cutoff point of 103CFU/mL;this allowed us to include only the most significantfindings and avoid contamination, and the combina-tion of this and the lack of induced sputum samplesmay have resulted in an underestimate of the num-ber of PPM isolates in the low CFU/mL samples.23-25

Our efforts to motivate patients to collect sputumsamples (a monthly sample per patient for 6 months)meant that the number of study subjects withouta sputum sample was small (eight patients). Anotherdrawback, the lack of a symptom diary, probably

than at least one admission in the previous yearpresents decreased discriminatory power, probablybecause there were fewer patients with multiplehospital admissions. Patel et al8observed that even

though the number of exacerbations was not relatedto bronchiectasis in their study, patients with bron-chiectasis did experience longer exacerbations. Thediscordance between these studies can be explainedby the fact that, in our study, only data from exac-erbations that required medical consultation wereincluded, and these were therefore more severe,

whereas the study by Patel and colleagues8collectedinformation from a symptom diary covering the fullseverity range of exacerbations.

Some variables that appeared as significant in thebivariate analysis, such as the presence of chronic

expectoration or the daily quantity of sputum pro-duced, or periods with prescribed antibiotics, were notincluded in the final model, even though these vari-ables are characteristic of bronchiectasis.29-31 Webelieve that there are two reasons for this: (1) the sig-

Table 5Forward Logistic Regression

Variables in the Equation

Univariate Analysis Adjusted Multivariate Analysis

OR (95% CI) PValue OR (95% CI) PValue

Severe COPD (FEV150%) 4.13 (1.71-9.94) .001 3.87 (1.38-10.5) .01PPM isolatesa 5.19 (2.08-12.9) .001 3.59 (1.3-9.9) .014At least one hospital admission in the previous y 3.07 (1.09-8.65) .024 3.07 (1.07-8.77) .037At least four acute antibiotic treatments 4.73 (1.26-17.7) .012 3.1 (0.58-15.5) .18Chronic expectoration 4.89 (1.5-15.86) .004 2.8 (1.02-7.7) .054Home oxygen therapy 4.12 (1.38-12.3) .007 1.1 (0.25-4.9) .89Fibrinogen, mg/dL 1.01 (1-1.01) .011 1.1 (0.99-1.01) .49Albumin, mg/dL 0.21 (0.05-0.86) .03 0.5 (0.08-3.02) .28

Variables included in the regression model and variables independently associated with the presence of bronchiectasis in patients with moderate tosevere COPD. Variables that were significant in the multivariate analysis are shown in bold. See Table 3 legend for expansion of abbreviation.aEight patients were unable to provide any sputum samples over the course of the study.

Figure1. Probability of the presence of bronchiectasis in patients with moderate to severe COPD, bypatient characteristics. PPM5potentially pathologic microorganism; prob5probability.


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fication of the specific phenotype of patients withCOPD and bronchiectasis, although further studiesare needed to evaluate whether the presence of bron-chiectasis worsens the prognosis of patients withCOPD. We believe that the results of this study willbe useful for estimating the probability of futurebronchiectasis in these patients and help guide earlytreatment, although the statistical model needs to be

validated by more wide-ranging studies.

Acknowledgments

Author contributions:Dr Martnez-Garca:contributed to thedesign of the study and the collection and analysis of the data; heis also the main author of the manuscript.Dr Soler-Catalua:contributed to the design of the study, the col-lection and analysis of the data, and review of the manuscript.Dr Donat Sanz:contributed to data collection and the writing ofthe manuscript.Dr Cataln Serra:contributed to data collection and the writingof the manuscript.Dr Agramunt Lerma:contributed to radiology and review of allthe images and review of the manuscript.

Dr Ballestn Vicente: contributed to radiology and review of allthe images and review of the manuscript.Dr Perpi-Tordera:contributed to the design and editing of themanuscript.Financial/nonfinancial disclosures:The authors have reportedto CHEST that no potential conflicts of interest exist with anycompanies/organizations whose products or services may be dis-cussed in this article.Role of sponsors: The sponsor had no role in the design of thestudy, the collection and analysis of the data, or in the preparationof the manuscript.

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Chest. 2002;121(suppl 5):151S-155S.2. Fuschillo S, De Felice A, Balzano G. Mucosal inflammationin idiopathic bronchiectasis: cellular and molecular mecha-nisms. Eur Respir J. 2008;31(2):396-406.

3. National Collaborating Center for Chronic Conditions.Chronic obstructive pulmonary disease. National clinical guide-line on management of chronic obstructive pulmonary dis-ease in adults in primary and secondary care. Thorax. 2004;59(suppl 1):1-232.

4. Martnez-Garca MA, Soler-Catalua JJ, Perpi-Tordera M,Romn-Snchez P, Soriano J. Factors associated with lungfunction decline in adult patients with stable non-cystic fibro-sis bronchiectasis. Chest. 2007;132(5):1565-1572.

5. Pea VS, Miravitlles M, Gabriel R, et al. Geographic variationsin prevalence and underdiagnosis of COPD: results of the

IBERPOC multicentre epidemiological study. Chest. 2000;118(4):981-989.

6. Miravitlles M, Soriano JB, Garca-Ro F, et al. Prevalence ofCOPD in Spain: impact of undiagnosed COPD on quality oflife and daily life activities. Thorax. 2009;64(10):863-868.

7. Weycker D, Edelsberg J, Oster G, Tino G. Prevalence andeconomic burden of bronchiectasis. Clin Pulm Med. 2005;12(4):205-209.

8. Patel IS, Vlahos I, Wilkinson TMA, et al. Bronchiectasis,exacerbation indices, and inflammation in chronic obstructivepulmonary disease.Am J Respir Crit Care Med. 2004;170(4):400-407.

9. OBrien CO, Guest PJ, Hill SL, Stockley RA. Physiologicaland radiological characterisation of patients diagnosed with

excluded information on less severe exacerbations.However, according to Patel et al,8it is possible thatthe frequency of these types of exacerbation is unre-lated to the presence of bronchiectasis in patients

with COPD, and, moreover, detailed informationon severe episodes was collected in our study. Fur-thermore, some causes of bronchiectasis could notbe ruled out with certainty, as no 24-h pH-metry

studies were performed to rule out gastroesophagealreflux disease. It is also sometimes impossible toknow whether the cause of bronchiectasis derivesfrom remote childhood infections, especially those ofa viral origin, although most causes of bronchiectasiscould be ruled out on the basis of the patients clinicalhistory and analytic data. Finally, 99% of the patientsin the present study were men. This can be explainedby our centers catchment area, which largely com-prises rural environments, meaning that many of thepatients are elderly. In the Spanish context, such asetting has a very low prevalence of smoking among

women, and this explains the high prevalence of menin the present study. Our conclusions cannot, there-fore, be extrapolated to women with COPD.

According to our results, there is a wide range ofpossibilities (as seen in Table 4), from the patient withsevere COPD, with an isolated PPM or chronic PPMcolonization in a respiratory sample or at least onehospital admission in the previous year, who wouldhave a 99% probability of presenting bronchiectasis,to the patient with moderate COPD who has noneof these characteristics and whose probability ofhaving bronchiectasis would be ,25%. Our results

therefore endorse the use of an HRCT scan to rule outthe presence of bronchiectasis in those patients withCOPD who have serious airflow obstruction, bron-chial colonization by PPMs (especially P aeruginosa),or previous exacerbations that required hospital-ization. Given the characteristics of the present study,

we cannot establish any conclusive causal relation-ship between COPD and bronchiectasis; nevertheless,it can be asserted that the presence of bronchiectasisin patients with COPD (of any cause) would requireearly treatment (especially with systemic antibiotics)and a more exhaustive microbiologic follow-up than

that indicated by the various guides published onbronchiectasis.In conclusion, according to our results from patients

with moderate to severe COPD, the presence ofsevere airflow obstruction, the isolation of a PPM ina sputum sample, and the need for at least one hospi-tal admission in the previous year are associated withbronchiectasis. When bronchiectasis is detected inpatients who present more severe functional COPD,32

with PPMs in the bronchial mucosa10and exacerba-tions (particularly serious ones33), their prognosis ispoorer; this underlines the need for the early identi-


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chronic obstructive pulmonary disease in primary care. Thorax.2000;55(8):635-642.

10. Wilkinson TMA, Patel IS, Wilks M, Donaldson GC,Wedzicha JA. Airway bacterial load and FEV1 decline inpatients with chronic obstructive pulmonary disease.Am JRespir Crit Care Med. 2003;167(8):1090-1095.

11. Sethi S, Maloney J, Grove L, Wrona C, Berenson CS. Airwayinflammation and bronchial bacterial colonization in chronicobstructive pulmonary disease.Am J Respir Crit Care Med .2006;173(9):991-998.

12. Zalacain R, Sobradillo V, Amilibia J, et al. Predisposing fac-tors to bacterial colonization in chronic obstructive pulmo-nary disease. Eur Respir J. 1999;13(2):343-348.

13. Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, DonaldsonGC, Wedzicha JA. Relationship between bacterial coloni-sation and the frequency, character, and severity of COPDexacerbations. Thorax. 2002;57(9):759-764.

14. Soler N, Ewig S, Torres A, Filella X, Gonzalez J, Zaubet A.Airway inflammation and bronchial microbial patterns inpatients with stable chronic obstructive pulmonary disease.Eur Respir J. 1999;14(5):1015-1022.

15. Banerjee D, Khair OA, Honeybourne D. Impact of sputumbacteria on airway inflammation and health status in clinicalstable COPD. Eur Respir J. 2004;23(5):685-691.

16. Kang EY, Miller RR, Mller NL. Bronchiectasis: comparisonof preoperative thin-section CT and pathologic findings inresected specimens. Radiology. 1995;195(3):649-654.

17. Hoffman EA, Simon BA, McLennan G. State of the Art.A structural and functional assessment of the lung viamultidetector-row computed tomography: phenotyping chronicobstructive pulmonary disease. Proc Am Thorac Soc. 2006;3(6):519-532.

18. Global Initiative for Chronic Obstructive Lung Disease. Globalstrategy for the diagnosis, management, and prevention ofchronic obstructive pulmonary disease. GOLD Web site.http://www.goldcopd.com/Guidelineitem.asp?l152&l251&intId52003. Update 2009. Accessed December 3, 2009.

19. Burge S, Wedzicha J. COPD exacerbations: definitions andclassifications. Eur Respir J. 2003;21(suppl 41):46s-53s.

20. Naidich DP, McCauley DI, Khouri NF, Stitik FP, Siegelman SS.Computed tomography of bronchiectasis. J Comput AssistTomogr. 1982;6(3):437-444.

21. Lynch DA, Newell JD, Tschomper BA, Cink TM, Newman LS,Bethel R. Uncomplicated asthma in adults: comparison of CTappearance of the lungs in asthmatic and healthy subjects.Radiology. 1993;188(3):829-833.

22. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW,Wedzicha JA. Usefulness of the Medical Research Council(MRC) dyspnoea scale as a measure of disability in patients

with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581-586.

23. Murphy TF, Brauer AL, Schiffmacher AT, Sethi S. Persistent

colonization by Haemophilus influenzae in chronic obstruc-tive pulmonary disease. Am J Respir Crit Care Med. 2004;170(3):266-272.

24. Chin CL, Manzel LJ, Lehman EE, et al. Haemophilus influ-enzae from patients with chronic obstructive pulmonary dis-ease exacerbation induce more inflammation than colonizers.

Am J Respir Crit Care Med. 2005;172(1):85-91.25. Sethi S, Evans N, Grant BJ, Murphy TF. New strains of

bacteria and exacerbations of chronic obstructive pulmonarydisease.N Engl J Med. 2002;347(7):465-471.

26. Cantn R, Cobos N, de Gracia J, et al. Tratamiento antimi-crobiano frente a la colonizacin pulmonar por Pseudomo-nas aeruginosa en el paciente con fibrosis qustica. ArchBronconeumol. 2005;41(suppl 1):1-25.

27. Cole PJ. Inflammation: a two-edged swordthe model ofbronchiectasis. Eur J Respir Dis Suppl. 1986;147:6-15.28. Garcia-Vidal C, Almagro P, Roman V, et al. Pseudomonas

aeruginosa in patients hospitalised for COPD exacerbation: aprospective study. Eur Respir J. 2009;34(5):1072-1078.

29. ODonnell AE. Bronchiectasis. Chest. 2008;134(4):815-823.30. Lazarus A, Myers J, Fuhrer G. Bronchiectasis in adults: a

review. Postgrad Med. 2008;120(3):113-121.31. Bilton D. Update on non-cystic fibrosis bronchiectasis. Curr

Opin Pulm Med. 2008;14(6):595-599.32. Celli BR, Cote CG, Marin JM, et al. The body-mass index,

airflow obstruction, dyspnea, and exercise capacity index inchronic obstructive pulmonary disease.N Engl J Med. 2004;350(10):1005-1012.

33. Soler-Catalua JJ, Martnez-Garca MA, Romn Snchez P,Salcedo E, Navarro M, Ochando R. Severe acute exacerba-tions and mortality in patients with chronic obstructive pul-monary disease. Thorax. 2005;60(11):925-931.
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