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1 Institutul National de Pneumoftiziologie "Marius Nasta" Bucharest, Romania, 2 Sociedad Española de la Patologia del Aparato Respiratorio, 3 Unit of Respiratory Intensive Care, Dept of Pulmonology, Clinical Institute of Pulmonology and Thoracic Surgery, Hospital Clinic, Institute of Biomedical Investigation August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain. 4 Abteilung für Pneumologie, Allergologie und Schlafmedizin, Medizinische Klinik und PolikIink Bergmannsheil, Klinikum der Ruhr-Universität, Bochum, Germany
CORRESPONDENCE: A. Torres, Servei de Pneumologia, Institut Clinic de Pneumologia i Cirurgia Toracica, Hospital Clinic i Provincial, Villarroel, 170, 08036, Barcelona, Spain. Fax: 34 932275454
Keywords: colonization, lung carcinoma, risk factors
Received: February 28, 2001
Accepted October 16, 2001
This study was supported by a fellowship of the European Respiratory Society and a grant from the Generalitat of Catalunya (1999SGR00228).
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Abstract |
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Forty-one patients with resectable lung cancer (22 (54%) active smokers, 52±23 pack-yrs) with a mean forced expiratory volume in one second of 80±16% predicted, were studied with bilateral protected specimen brush and lung tissue biopsy during the surgical procedure. Quantitative bacterial culture, susceptibility tests and histological examination of samples were performed.
Bronchial colonization with 
1 potential pathogenic micro-organism was found in 17 of 41 (41%) patients. The most frequent strains isolated were: Haemophilus influenzae (35%), Streptococcus pneumoniae (13%) and Pseudomonas spp. (9%). The risk factors for bronchial colonization were central location of the tumour (odds ratio (OR)=9.2, confidence interval (CI) 95%=2.1–39.6, p=0.003) and increased body mass index (OR=1.6, CI 95%=1.2–2.2, p=0.005). The frequency of postoperative infectious pulmonary complications was low (five cases (12%)) and no relationship was observed with bronchial colonization.
Patients with resectable lung carcinoma had a high rate of bronchial colonization (41%), mainly with potential pathogenic microorganisms. The independent risk factors for colonization in these patients were central location of the tumour and a high body mass index.
Improved methods for early detection of lung cancer have allowed an increasing number of patients to benefit from surgical treatment. Nevertheless, a concomitant increased risk of pulmonary complications and death has been reported in these patients 1. Swartz et al. 2 found a perioperative mortality rate of 10.9% after pneumonectomy. Nosocomial pneumonia is one of the main causes of postoperative mortality 3, with several factors related to this condition, such as surgical stress, nutritional status, cancer-related immunosuppression and pre-existing diseases (chronic obstructive pulmonary disease (COPD), diabetes mellitus, etc.) 4, 5.
Bronchial bacterial colonization may be frequent in patients with lung cancer as most of these patients have underlying COPD, which is known to be associated with a high colonization rate. For example, Monso et al. 6 found a colonization rate of 25% in patients with stable COPD. Very few studies have investigated the pattern of distal airway colonization in patients with bronchial carcinoma. Cabello et al. 7 reported that 42% of patients with pulmonary carcinoma had bronchial colonization with commensal or potential pathogenic micro-organisms (PPMs). Although there is evidence of the role of bronchial colonization and the subsequent development of nosocomial pneumonia in intensive-care unit patients 8, no data are available on this relationship in patients after lung cancer resection.
Since this field has been investigated less than colonization in patients with COPD or bronchiectasis, the aims of this study were to establish the profile of bronchial colonization in patients with resectable lung cancer and to determine the risk factors associated with this condition, in order to increase understanding of the aetiology and prevention of postoperative infective pulmonary complications in patients undergoing lung resection.
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Material and methods |
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Study design
The patients' characteristics (age, sex, smoking habits (pack-yrs), alcohol (g·day–1), comorbidity, Karnofsky index, and body mass index (BMI)) were recorded before surgery (table 1
). Lung function tests (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusion capacity for carbon monoxide (DL,CO) and gas exchange) and computed tomography (CT) scan for TNM staging were performed in all of the patients. The cell type of the tumour was established from pre-operative histological examination of a lung tissue sample obtained by bronchoscopic biopsy or CT-guided transthoracic needle biopsy.
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Procedures
Bronchoscopy (fibreoptic bronchoscope BF30; Olympus, New Hyde Park, NY, USA) was performed perioperatively, after anaesthesia and endotracheal intubation and before proceeding to the surgical intervention. Tumour location was considered central if it was accessible by bronchoscopy, and peripheral when there was no bronchoscopic evidence of an endobronchial tumour 9. A PSB technique (Microbiology brush, Mill-Rose Laboratory Inc. 7310, Mentor, OH, USA) was used for sampling bronchial secretions from the site of the tumour (pre-obstructive area) and from the contralateral lung. Each sample was collected in 1 mL sterile saline solution and then diluted at 10–1, 10–2, 10–3 and inoculated on standard media: blood agar, chocolate, Centre for Disease Control (CDC)-agar, McConkey, Sabouraud and Lowenstein, in aerobic and anaerobic conditions. Cultures were evaluated after 24 h, 48 h, 7 days (for CDC, blood agar) and 4–8 weeks (for Sabouraud and Lowenstein).
After surgical resection, a sample of the tumour and a sample of the post-tumoural area (dimension 2x2x2 cm) were collected under sterile conditions. The latter was divided into two equal fragments, one for microbiological investigation and the other for histological examination. Quantitative cultures were performed with all secretions and lung tissue samples. A cut-off of 102 colony forming units (cfu)·mL–1 was used to define colonization 7. Susceptibility tests using the E-test method were carried out for positive growth. Bacteria were classified as PPMs and non-PPMs as described elsewhere 7. The PPM group included the micro-organisms usually responsible for respiratory infections (e.g. Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa). Non-PPMs are micro-organisms of the oropharyngeal and gastrointestinal flora, which do not cause infection in nonimmunosuppressed patients (e.g. Streptococcus viridans, Neisseria spp., Corynebacterium spp., Candida spp.).
The histological findings of the lung tissue were classified into five categories: 1) postobstructive changes: chronic inflammation and desquamative alveolar damage, without fibrosis; 2) fibrosis: presence of connective tissue and collagen; 3) lymphangitis: neoplasic infiltrate of the lymphatis; 4) granuloma: foci of giant cells without necrosis; 5) pneumonia: neutrophilic infiltration in the alveoli. After bronchoscopy, each patient received prophylactic antibiotic treatment according to hospital policy (i.v. cefazoline 1 g x3, or clindamycin 300 mg x4, for 48 h).
Statistical analysis
Data processing and analysis were performed using the SPSS 10.0 for Windows (SPSS, Chicago, IL, USA). The results are expressed as percentage and mean±sd. Continuous variables were compared using a nonparametric test (Mann-Whitney, U-test) and the categorical variables by Chi-squared or the Fisher exact test, as appropriate. The level of significance was set at 5%. Logistic regressions were performed to evaluate the risk factors associated with bronchial colonization and the risk factors associated with postoperative infective pulmonary complications. Variables with a p<0.10 in one univariate analysis were included in the multivariate analysis.
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Results |
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. Tumour location was central (accessible by bronchoscopy) in 15 cases (37%) and peripheral in 26 patients (63%).
Prevalence and pattern of bronchial colonization
The PSB and lung tissue cultures showed a total of 23 strains (21 PPMs and two non-PPMs, corresponding to 10 different species) in 17 (41%) of the 41 patients. Of the 10 different species isolated, eight were PPMs while two were non-PPMs. The PPMs isolated were: eight H. influenzae, three S. pneumoniae, three Pseudomonas spp., two M. catarrhalis, two S. aureus, one Enterobacter spp., one Mycobacterium gordonae and one Eikenella corrodens. The non-PPMs isolated were: one S. viridans and one plasma coagulase-negative Staphylococcus (table 2). When considering PSB cultures alone a total of 20 strains were identified in 16 patients (39%). Resection lung samples of the 41 patients showed only three strains in the cultures (13% of all isolated strains; M. gordonae, E. corrodens (102 cfu·ml–1 in both tumour and non-tumour lung samples) and coagulase-negative Staphylococcus (102 cfu·ml–1 in tumour), which were not recovered in PSB samples, giving an additional airway colonization rate of 2%.
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). Bilateral PSB sampling showed the following results: of the 41 patients three (7%) had bronchial colonization only on the side of the tumour, four (10%) had only colonization of the contralateral lung (opposite the tumour) and in eight (20%), colonization was bilateral. In the last group, of the 41 patients, six (14%) showed the same micro-organism on both sides and two (5%) had a different colonization profile.
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), except for one oxacillin-resistant strain of S. aureus and two ß-lactamase positive strains of H. influenzae and M. catarrhalis, respectively (both isolated in the same patient). No multiresistant micro-organism was found.
Histological findings
Histological examination of the post-tumoural tissue was performed in all 41 patients. No pathological findings were seen in 21 patients (52%), postobstructive changes were seen in 15 cases (35%), fibrosis in two cases (5%), granuloma in two cases (5%) and lymphangitis in one patient (3%). Of the 17 patients with airway colonization, seven (41%) showed no pathological findings, eight (47%) had postobstructive changes, one patient (6%) had granuloma and one patient (6%) had lymphangitis. In the patient with histological granuloma as seen in the lung samples, no mycobacteria were isolated from their respiratory samples.
Risk factors for bronchial bacterial colonization
In the univariate analysis, airway colonization by PPMs was considered as the dependant variable, with potentially predictive variables being: age (>65 yrs), sex (male/female), smoking habits (smokers/exsmokers; >40 pack-yrs), hospitalization during the last year, BMI>25, FEV1<65%, DL,CO<70% and tumour location (central/peripheral). Only two of these variables proved to be statistically significant: BMI>25 (p=0.01) and central versus peripheral tumour location (p=0.002). Furthermore, the logistic regression model used to determine the predictors of bronchial bacterial colonization showed that central location of the tumour and increased BMI were independent risk factors for colonization (table 4). Central tumours were associated with a greater risk (OR=9.2, CI (95%)=2.1–39.6, p=0.003) for colonization than peripheral tumours. Increased BMI>25 showed an OR=1.13, CI (95%)=1.2–2.2 (p=0.005).
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Risk factors for infectious pulmonary complications
FEV1<65%, DL,CO<70%, BMI<25, age>65 yrs and bronchial colonization were analysed as potential risk factors for postoperative infectious pulmonary complications. None of these variables was significant on univariate analysis (table 5). Bronchial colonization was not a statistically significant predictor of infectious complications.
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Discussion |
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TOPAbstractMaterial and methodsResultsDiscussionReferences |
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There are few data available in the literature regarding bronchial colonization in patients with lung cancer. Most studies on airway colonization refer to patients with COPD, with rates of bacterial colonization in such cases ranging from 25–83% 6, 7, 10–13. Cabello et al. 7 also included patients with bronchogenic carcinoma, finding a colonization rate of 42%. In this study, a higher rate of PPMs was found isolated in the PSB samples compared to Cabello et al. 7. This finding may be related to the previous hospitalization period (3±1 days) in the present series, as the patients observed in Cabello et al. 7 were investigated before admission to the hospital. It is well known that prior hospitalization is a risk factor for abnormal colonization, at least in critically ill patients 14. Further prospective studies would be required to confirm this hypothesis.
The pattern of bronchial colonization in this study's patients appeared to be similar to that found in patients with chronic bronchitis or in smokers 15, which is not surprising as all of the patients were smokers or exsmokers and 42% had an FEV1<80%. No significant relationship between colonization and obstruction, or the number of pack-yrs was found. However, a population of lung cancer patients were investigated with well preserved lung function and a mean FEV1, which was normal, and this may explain why FEV1 was not a risk factor for colonization.
Lung tissue culture was positive in only three cases (7% of the patients). This finding is consistent with other studies 16, 17, which have reported a low rate of microbial growth in lung tissue in patients with lung cancer. In the study by Yuang-Shuang et al. 16 on the bacteriology of obstructive pneumonitis, the rate of positive culture of postobstructive lung tissue was 12% in nonfebrile patients with lung cancer. The micro-organisms isolated in lung tissue in the study by Yuang-Shuang et al. 16 were all PPMs, corroborating the findings in the present study. Furthermore, a recent study 17 on the bacteriology of cavitating lung tumours showed that only one (7%) of 15 nonfebrile patients had a positive culture of transthoracic aspirate.
Susceptibility tests showed no resistance to the usual antibiotics, except for one strain of H. influenzae and one of M. catarrhalis, which were ß-lactamase positive, and one oxacillin-resistant S. aureus. These results are in contrast to other studies that found antibiotic resistance in 32–50% 18, 19 of the patients. This difference could be explained by the fact that most of the patients in the present study had well-preserved lung function while patients in other studies had a significant degree of airway obstruction, associated with severe exacerbation and frequent antibiotic treatment which may have led to antibiotic resistance 20.
Central location of the tumour was an independent risk factor for global bronchial colonization (OR=9.2) compared to peripheral location, probably due to the mechanical bronchial obstruction associated with such tumours. The authors suggest that unilateral obstruction may be a predisposing factor for accumulation of secretions above the obstructed airway and consequent aspiration of colonized secretions to the contralateral lung.
Increased BMI>25 was also an independent risk factor for bronchial colonization, but the OR was small (1.6) compared to tumour location. This finding could be explained by decreased diaphragmatic motility in obese patients, which facilitates the accumulation of bronchial secretions and subsequent microbial growth. There is strong evidence that elevated BMI is also a risk factor for survival in patients with lung carcinoma 21 and for postoperative complications in thoracic, abdominal and vascular surgery 5.
The most common histological findings in regard to postobstruction were chronic inflammatory changes (47% in the colonized patients and 29% in the noncolonized patients). No histological evidence of pneumonia, namely neutrophilic infiltration in alveoli, was found. In fact, none of the patients was febrile at any time and no radiological change was observed during follow-up. As previous studies 16, 17 have shown, pneumonia or lung abscess rarely occur in nonfebrile patients with lung cancer.
Only 12% of the patients developed postoperative infective complications: 5% had tracheobronchitis and 7% bronchopleural fistulae with empyema. No episode of nosocomial pneumonia was observed in these patients, although in the literature the incidence of nosocomial pneumonia in post-thoracotomy patients ranges between 5–22% 3, 22. The difference may be explained, in part, by effective prophylaxis with cefazoline administered perioperatively and during the following 48 h in all the patients. Another explanation may be that postoperative pneumonias may not have been detected due to the small sample size.
Several risk factors have been reported for postoperative infective pulmonary complications, including FEV1, low BMI, increased age, active smoking, DL,CO<70% and bronchial obstruction 23–25. In this analysis, no variable was associated with pulmonary complications. Bronchial colonization was not associated with infective pulmonary complications with a similar percentage of pulmonary infections in colonized and noncolonized patients, 12% versus 14% respectively. However, a larger sample of patients is needed to assess the potential relationship between bronchial colonization and postoperative pulmonary infections.
In summary, the present study demonstrates that patients with resectable lung carcinoma show a high rate of bronchial colonization (41%), mainly with potentially pathogenic organisms. Independent risk factors for colonization in these patients were central location of the tumour and an elevated body mass index.
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