Postoperative Pneumonia after Major Lung Resection

Abstract

Section:

Background: Postoperative pneumonia (POP) is a life-threatening complication of lung resection. The incidence, causative bacteria, predisposing factors, and outcome are poorly understood.

Design: Prospective observational study.

Methods: A prospective study of all patients undergoing major lung resections for noninfectious disease was performed over a 6-mo period. Culture of intraoperative bronchial aspirates was systematically performed. All patients with suspicion of pneumonia underwent bronchoscopic sampling and culture before antibiotherapy.

Results: One hundred and sixty-eight patients were included in the study. Bronchial colonization was identified in 31 of 136 patients (22.8%) on analysis of intraoperative samples. The incidence of POP was 25% (42 of 168). Microbiologically documented and nondocumented pneumonias were recorded in 24 and 18 cases, respectively. Haemophilus species, Streptococcus species, and, to a much lesser extent, Pseudomonas and Serratia species were the most frequently identified pathogens. Among colonized and noncolonized patients, POP occurred in 15 of 31 and 20 of 105 cases, respectively (p = 0.0010; relative risk, 2.54). Death occurred in 8 of 42 patients who developed POP and in 3 of 126 of patients who did not (p = 0.0012). Patients with POP required noninvasive ventilation or reintubation more frequently than patients who did not develop POP (p < 0.0000001 and p = 0.00075, respectively). POP was associated with longer intensive care unit and hospital stay (p < 0.0000001 and p = 0.0000005, respectively). Multivariate analysis showed that chronic obstructive pulmonary disease, extent of resection, presence of intraoperative bronchial colonization, and male sex were independent risk factors for POP.

Conclusions: Pneumonia acquired in-hospital represents a relatively frequent complication of lung resections, associated with an important percentage of postoperative morbidity and mortality.

Keywords:

colonization; lung resection; postoperative pneumonia; risk factors; thoracic surgery

Major lung resection carries high morbidity and significant mortality (1–3). It has been generally believed that bronchopleural fistulas and respiratory failure are the most important determinants of postoperative morbidity and mortality.

It has been shown that, among all types of surgery, noncardiac thoracic surgical procedures are frequently complicated by postoperative pneumonia (POP) (4). POP is especially severe after thoracic surgery and is associated with high mortality (5).

The exact incidence of POP after lung resection is, paradoxically, poorly known; the risk factors and causative pathogens have been rarely investigated and little is known about the pathophysiology of POP (6–11). Furthermore, POP may be difficult to diagnose because of the frequent occurrence of fever, hypoxemia, or abnormal chest X-ray after lung resection. As a consequence, strict criteria (including clinical aspect, radiographic abnormalities, laboratory results, and culture of representative specimens) have been used only rarely to define this entity. Part of our current knowledge is derived from retrospective series (1, 12–30) (Table 1). Few prospective studies (2, 7, 10, 11, 31–52) (Table 2) have been performed, most with important limitations.

TABLE 1. **RETROSPECTIVE STUDIES ON POSTOPERATIVE PNEUMONIA AFTER LUNG SURGERY**
Ref.	Targeted Study?	Particularity of Study	No. Patients	Type of Resection	Antibioprophylaxis	Follow-up Duration	Definition of Pneumonia	Microbiology	Need for Antibiotherapy	Incidence of Pneumonia (%)
1	No	—	639	P	NS	30	No	NS	NS	10.2
12	No	—	242	P	Cefuroxime, 24 h	30	Yes	NS	NS	3.3
13	No	—	344	LR	NS	30	No	NS	NS	19
14	No	—	61	Seg	NS	30	No	NS	NS	14
15	No	—	108	Sleeve L	NS	NS	No	NS	NS	10.2
16	No	—	350	LR	NS	NS	No	NS	NS	5.1
17	Yes	—	261	P	NS	30	Yes	NS	NS	12.8
18	Yes	Postchemotherapy	69	LR	NS	30	No	NS	NS	19
19	No	—	335	L or P	NS	30	No	NS	NS	9.8
20	Yes	—	89	LR	NS	30	No	NS	NS	2.2
21	Yes	—	266	LR	NS	NS	Yes	Yes	NS	7.4
22	No	—	209	P	NS	30	No	NS	NS	5.1
23	Yes	Patients > 80 yr	37	LR	NS	30	No	NS	NS	11.4
24	No	—	143	Sleeve P	NS	30	No	NS	NS	7.8
25	No	—	291	LR	NS	30	No	NS	NS	2.1
26	Yes	—	101	LR	NS	NS	Yes	NS	NS	22
27	No	—	197	P	NS	NS	Yes	NS	NS	22^*
28	No	—	141	Sleeve L	NS	30	No	NS	NS	6.7
29	No	—	197	P	NS	30	No	NS	NS	6.6
30	No	—	369	L	NS	30	No	NS	NS	29^*

Definition of abbreviations: L = lobectomy; LR = lung resection; NS = not stated; P = pneumonectomy; Seg = segmentectomy.

^* Incidence of respiratory infection with isolations of pathogens.

TABLE 2. **PROSPECTIVE STUDIES ON POSTOPERATIVE PNEUMONIA AFTER LUNG SURGERY**
Ref.	Targeted Study?	Particularity of Study	Patient No.	Type of Resection	Antibioprophylaxis	Follow-up Duration (d)	Definition of POP	Microbiology of POP	Need for Antibiotherapy	Incidence of Pneumonia
2	Yes	Lung cancer	60/60	L or P	Sulbactam–ampicillin s.shot/cefazolin s.shot	3	Yes	No	NS	3.3%/16.6%
7	Yes	—	194	LR	Cefuroxime 24 h	3	Yes	Yes^*	20.7%	17%
10	Yes	—	54	L or P	Cefuroxime 48 h	10	No	No	NS	13%
11	Yes	—	60/60	LR	Cefuroxime 24 h/doxycycline 5 d	NS	Yes	No	27%/30%	10%/18%
31	Yes	—	50/52	LR	Cefuroxime 48 h/cefepime 24 h	NS	Yes	Yes^†	NS	12%/15.3%
32	No	Lung cancer	306	LR	Cefuroxime 24 h	NS	Yes	No	NS	8.6%
33	No	Lung cancer	52	L or P	Fluoxacillin 48 h	30	Yes	No	NS	24.5%
34	Yes	—	62	L or P	NS	NS	No	No	NS	8%
35	No	—	500	LR	Cefamandol 48 h	NS	Yes	No	NS	22%
36	Yes	—	44	LR	NS	30	Yes	No	NS	25%
37	No	FEV₁ < 40%	65	L or P	NS	NS	Yes	No	NS	9.2%
38	Yes	—	61	L or P	NS	NS	Yes	No	NS	6.4%
39	No	—	605	LR	NS	30	No	No	NS	5.3%
40	No	Lung cancer	136	P	NS	NS	No	No	NS	5.8%
41	No	—	783	LR	NS	30	No	No	NS	6.4%
42	No	—	331	LR	NS	NS	No	No	NS	2%
43	Yes	—	100/100	LR	Cefuroxime 24 h/cefuroxime 48 h	8	Yes	Yes^‡	NS	30%/15%
44	Yes	Lung cancer	117	LR	NS	21	Yes	No	NS	37%^¶
45	Yes	—	30/30	LR	Sulbactam–ampicillin s.shot/72 h	NS	Yes	No	NS	13%/20%
46	Yes	—	48/46	LR	Penicillin G/cefuroxime	10	Yes	No	35%/22%	27%/17%
47	Yes	—	100/89	LR	Cefazolin s.shot /cefazolin 48 h	30	Yes	No	12%/13%	8%/8%
48	Yes	No infection	70/50	LR	Cefazolin s.shot/No	NS	No	No	NS	4%/8%
49	Yes	—	118/91	LR	Cefalotin 24 h/No	NS	Yes	Yes^§	NS	14%/27%
50	Yes	—	45/47	LR	Penicillin 36 h/No	NS	Yes	No	94%/80%	40%/33%
64	Yes	Major lung resection in 50% of cases	295	LR	Cefotaxime 48 h or amoxicillin–clavulanate (3 g) 48 h	30	Yes	Yes^§	NS	2.7% (but 16% lower respiratory tract infection)
65	Yes	Lung cancer	78	LR	Cefazolin 24 h	NS	Yes	Yes^‖	NS	12% (and 24% of bronchitis)

Definition of abbreviations: L = lobectomy; LR = lung resection; Lung cancer = lung cancer only; No = no antibioprophylaxis was administered; No infection = infected patients or patients undergoing major lung resection for infectious disease were excluded; NS = not stated; P = pneumonectomy; POP = postoperative pneumonia; s.shot = single shot of prophylaxis.

Among the 20 prospective studies concerning POP, 16 were specifically targeted and a definition of POP was provided in 13 studies. In only four studies were data concerning involved pathogens provided, although different types of specimens were analyzed.

^* Microbiological studies were carried out on sputum samples. Approximately 50% of patients had preoperative antibiotherapy.

^† Specimens for microbiological examination included chest drain and sputum.

^‡ Specimens for microbiological examination included sputum, chest drain, pleural fluid, and blood.

^§ The kind of specimen for microbiological examination was not precisely given.

^‖ Cultures were carried out on sputum samples.

^¶ Incidence of all respiratory complications.

Patients undergoing major lung resections carry many risk factors for nosocomial pneumonia, including a frequent smoking history (4, 17, 53), coexistent chronic bronchitis or chronic obstructive pulmonary disease (COPD) (1, 12, 54), neoplastic disease, frequent extrathoracic comorbidities (6), and poor nutritional status (1, 33). Last, but not least, surgery involves the respiratory system itself with anesthesiologic and surgical implications. Postoperative administration of opioids in patients with a recent amputation of lung tissue may further induce hypoventilation with possibly related complications (6).

We performed a 6-mo prospective study including all consecutive patients undergoing major lung resection for noninfectious diseases to investigate the incidence and the characteristics of POP, the risk factors (including the presence of intraoperative airway bacterial colonization), and the outcome.

METHODS

Section:

Patients

All patients undergoing major lung resection between June 15, 2001, and December 15, 2001, for noninfectious disease and without signs of acute respiratory infections were eligible for this study. Patients treated with antibiotics (because of respiratory or extrarespiratory infections) in the week preceding surgery were excluded from the study. Patients presenting at the date of admission for planned surgery with clinical and radiologic signs of pulmonary infection (fever greater than 38°C, purulent sputum) were excluded from this study in case surgery was urgent. In other cases, they received antibiotic treatment as outpatients and secondarily were readmitted for the planned surgery after at least 1 wk of discontinued antibiotherapy. These last patients were included in the study. Patients receiving antibioprophylaxis other than cefamandol were analyzed separately. Patients eligible for entry into the study entry but receiving explorative thoracotomy or sublobar resections because of intraoperative findings were excluded from the study.

Informed consent was obtained from all patients. The research was conducted according to recommendations outlined in the Helsinki Declaration.

Study Design

All the data concerning patient characteristics, results of microbiological studies, treatment procedures, and outcome were prospectively collected by means of a standardized questionnaire. Three sections (concerning patient characteristics and risk factors for POP, intraoperative events, and postoperative outcome) were to be filled out. Most patients were hospitalized the day before surgery for preoperative surgical and anesthetic assessment. Surgery had been scheduled in all the cases during a preoperative visit to the outpatient clinic.

Information about age, sex, weight, lung function, indication for lung resection, Karnofsky index, and C-reactive protein level was collected. White blood cell count (WBC), chest X-ray, and clinical examination were systematically performed to eliminate the possibility of underlying pneumonia or bronchitis. Nutritional status was assessed by determination of body mass index and evaluation of possible weight loss in the previous 6 mo. Lung function was evaluated by spirometry and, in almost all the cases, by calculation of predictive postoperative function with perfusion lung scanning.

We studied the following risk factors for POP:

Already reported risk factors (1, 4, 6, 12, 17, 33, 53, 54): age greater than 70 yr (4); weight loss in the last 6 mo (4, 33); associated respiratory diseases, such as chronic bronchitis or COPD (1, 4, 12, 54); smoking habit (active or past smokers [stopped for more than 2 mo]) (1, 4, 17, 53); alcohol intake greater than two drinks per day in the past 2 wk (1); past head and neck surgery (4, 6); global score for risk of POP, as established by Arozullah and coworkers (4).
Possible risks for POP, not necessarily confirmed by previous studies: obesity (body mass index greater than 25), American Society of Anesthesiology score, comorbidities (including diabetes mellitus [4], chronic renal insufficiency [4], previous radiotherapy, neoadjuvant chemotherapy [1, 16, 18, 19, 55, 56], and chronic cardiac insufficiency [systolic ejection fraction lower than 50% at echocardiography]) (6), sputum retention, and noninvasive ventilation before POP.

All patients were intubated with a double-lumen endobronchial tube to perform single-lung ventilation. Immediately after insertion of the tube, bilateral bronchial aspirations were performed. Quantitative endobronchial aspirate samples were obtained with a sterile suction catheter equipped with a mucus collection tube (design 534-16; Vygon, Ecouen, France). The catheter was introduced through each channel of the double-lumen tube and was blindly advanced at least 30 cm before suctioning. No liquid was instilled. Intraoperative bronchial aspirates were sent to the microbiology laboratory within 15 min of collection. A patient was considered colonized if quantitative endobronchial aspirate culture at 48 h was positive with a predominant germ (i.e., pathogenic bacterial species) exceeding a cutoff value of 10⁴ cfu/ml in at least one side.

Patients received antibiotic prophylaxis with a second-generation cephalosporin (cefamandol, 1.5 g at the induction of anesthesia and postoperatively, 3 g/24 h for 48 h) except in the case of known or suspected allergy, or if a different type of prophylaxis was indicated (e.g., in the case of valve disease).

Lung resections were performed according to standard techniques. Side, type of resection, possible associated sleeve bronchial or chest wall resection, previous thoracotomy, and total procedure time were recorded. A policy of early extubation was systematically employed. Decisions concerning intensive care unit (ICU) hospitalization after resection were established on the basis of type and extent of resection, predicted postoperative lung function, and associated comorbidities.

Duration of ICU stay, as well as the therapeutic intensity score in ICU (OMEGA) (57, 58), were recorded prospectively. The OMEGA score takes into account several variables related to ICU stay, including duration of invasive or noninvasive mechanical ventilation and presence of hemodynamic impairment. It has been shown that it strongly correlates with total ICU costs, medical costs, and nursing requirements (58). Postoperative analgesia was achieved by one of the following methods: patient-controlled analgesia (morphine), or spinal or thoracic epidural analgesia. Patients were kept in the semirecumbent position. A regular program of physiotherapy was started on the day of operation. Oral alimentation was started on Postoperative Day 1 after lobectomy and on the second day after pneumonectomy. In cases of previous head and neck surgery or if recurrent nerve paralysis was observed, a special program for realimentation was started.

Outcome Assessment

Patients were examined twice per day, and measurement of C-reactive protein and WBC was performed on Days 0, 1, 4, 8, and 10. Chest roentgenograms were done postoperatively once per day during the period of chest drainage. Our general policy was to maintain a high index of clinical suspicion for POP and to try to identify the bacteria involved by quantitative fiberoptic bronchoscopy aspiration and/or plugged telescopic catheter and/or protected specimen brush sampling. Thus, fiberoptic bronchoscopy samples were systematically obtained before antibiotic therapy in every patient who presented clinical signs of pneumonia: (1) abnormal radiographic findings (new or changing radiographic infiltrates that persisted after physiotherapy or bronchoaspiration), (2) fever greater than 38°C, and (3) one of the following criteria: a new rise in C-reactive protein value or WBC count over the last 24 h (with WBC greater than 12 × 10⁹/L) or an increase and modification of the expectorate, possibly with purulent aspect. Patients with positive plugged telescopic catheter sample (more than 10³ cfu/ml), protected specimen brush sample (more than 10³ cfu/ml), or positive blood culture represented the “documented POP” group. If the significant cutoff values were not reached, but clinical and radiologic improvement occurred after the administration of antibiotics, patients were considered as having “nondocumented POP.” Acute bronchitis was defined as an increase and modification of sputum (purulent) with a laboratory criterion (predominant bacteria greater than 10⁷ cfu/ml at sputum culture or greater than 10⁵ cfu/ml at bronchoaspiration) and without radiologic abnormalities. All lobar atelectases resistant to physiotherapy were explored by fiberoptic bronchoscopy with bacteriologic sampling. Chest X-ray was obtained immediately thereafter to ensure reventilation of lung parenchyma and to either confirm or rule out atelectasis. All postoperative pulmonary complications were reviewed secondarily by a pneumologist, a surgeon, and an intensive care physician. Infections occurring within 1 mo of surgery were recorded. Wound infection was defined as a reddened, painful, and indurated wound not necessarily associated with bacteria isolation. Empyema was defined as the presence of purulent fluid in the pleural drainage or as the isolation of pathogens from the pleural cavity. Other nosocomial infections were defined according to standard definitions (Centers for Disease Control and Prevention, Atlanta, GA). Need for antibiotics other than antibiotic prophylaxis was also recorded.

Statistical Analysis

Results are expressed as percentages and means ± SD. Continuous variables were compared by nonparametric test (Mann-Whitney) and categorical variables by the χ² or Fisher's exact test as appropriate. Data processing and analysis were performed with the statistical software system SEM (Silex Development, Mirefleurs, France). A p value less than 0.05 was considered significant. The risk factors found to be predictive of POP at univariate analysis were entered into a multivariate regression analysis, to identify independent variables.

RESULTS

Section:

Between June 2001, and December 2001, 168 of 186 patients undergoing major lung resections in our department were included in the study.

Eleven patients were excluded from the study because of a preexisting infection at the time of operation (chronically suppurating bronchiectasis, n = 4; tuberculosis, n = 2; other mycobacterial infection, n = 1; infected tumor under antibiotherapy, n = 4). Patients with chronically suppurating bronchiectasis and infected tumors were hospitalized for surgery while already undergoing treatment by targeted antibiotherapy, which was further continued postoperatively. Patients with mycobacterial infections were excluded from the study because of possible interference with the aim of the study by systematic pre- and postoperative antimycobacterial therapy. Antibioprophylaxis with drugs different from cefamandol was employed in seven patients because of known allergy to penicillin/cephalosporins or because coexistent cardiac valve disease was indicated. POP occurred in three of them (microbiologically proven in one case) and was responsible for one death.

Demographic data of the remaining 168 patients, principal known risk factors of POP, and surgical procedures are shown in Table 3. The global score for risk of POP established by Arozullah and coworkers (4) was 32.3 ± 7.6. The main indication for major lung resection was non–small cell lung cancer. Thirty-six of 168 patients had received neoadjuvant chemotherapy.

TABLE 3. **PREOPERATIVE CLINICAL STATUS AND PREOPERATIVE RISK FACTORS FOR POSTOPERATIVE PNEUMONIA**
Parameter	Value
Preoperative clinical status
Age, yr, mean ± SD	60.8 ± 11.9
Males, no. (%)	139 (82.7)
Weight (kg), mean ± SD	71.3 ± 15.2
Karnofsky index score, mean ± SD	90.7 ± 10.2
Malignant disease, no. (%)	161 (95.8)
NSCLC, no. (%)	152 (90.5)
Preoperative risk factors for POP
POP risk index (points), mean ± SD^*	32.3 ± 7.6
Age ⩾ 70 yr, no. (%)	42 (25.0)
Body mass index ⩾ 25, no. (%)	67 (39.9)
Weight loss ⩾ 10%, no. (%)	30 (17.8)
Smoking history, no. (%)	143 (85.1)
Smoking cessation ⩾ 60 d, no. (%)	79 (47)
Alcohol, no. (%)	29 (17.3)
FEV₁ ⩽ 80% of predicted, no. (%)	71 (42.26)
COPD^†
At risk (stage 0), no. (%)	25 (14.9)
Mild (stage I), no. (%)	13 (7.7)
Moderate (stage II), no. (%)	31 (18.4)
Severe (stage III), no. (%)	0
Diabetes mellitus, no. (%)	19 (11.3)
Chronic renal insufficiency, no. (%)	3 (1.8)
Preoperative chemotherapy, no. (%)	36 (21.4)
Previous radiotherapy, no. (%)	6 (3.6)
Previous head and neck surgery, no. (%)	2 (1.2)
ASA III+IV, no. (%)	57 (33.9)
Preoperative CRP ⩾ 20 mg/ml, no. (%)	38 (22.6)
Details of operations
Lobectomy, no. (%)	128 (76.2)
Pneumonectomy, no. (%)	38 (22.6)
Sleeve resection, no. (%)	9 (5.3)
En bloc chest wall resection, no. (%)	6 (3.6)
Previous thoracotomy, no. (%)	10 (5.9)
Procedure time (min), mean ± SD	183 ± 61
NIV before POP, no. (%)	13 (7.7)
Reintubation before POP, no. (%)	0

Definition of abbreviations: ASA = American Society of Anesthesiology score; COPD = chronic obstructive pulmonary disease; CRP = C-reactive protein; NIV = noninvasive ventilation; NSCLC = non–small cell lung cancer; POP = postoperative pneumonia.

Number of patients surveyed: 168.

^* Score for risk of POP was established according to Arozullah and coworkers (4).

^† COPD was defined according to Pauwels and coworkers (59).

One hundred and thirty-six (80.9%) patients underwent bilateral intraoperative bronchial aspiration. No growth was observed in 30 of 136 (22.1%) patients, whereas in 75 of 136 (55.1%) cases germ growth not reaching the defined threshold of colonization was observed. Colonization with predominant bacteria (at least 10⁴ cfu/ml) was identified in 31 of 136 cases (22.8%). Haemophilus and Streptococcus species represented the most frequently involved microorganism (Table 4, column 1). Pseudomonas species or gram-negative enteric bacilli were cultured in six cases. Polymicrobial colonization was proven in nine patients. Five of 19 (26.3%) cultured Haemophilus strains were found positive for β-lactamase, whereas two of nine Streptococcus pneumoniae (22.2%) had a decreased sensitivity to penicillin G (minimal inhibitory concentration [MIC] > 0.06 mg/L).

TABLE 4. **BACTERIA RECOVERED FROM INTRAOPERATIVE SAMPLES AND INVOLVED IN VARIOUS CASES OF DOCUMENTED POSTOPERATIVE PNEUMONIA**
	Intraoperative Bacterial Colonization^‡	Pathogenic Bacteria of POP^§	p Value
No. patients with QEBA-positive samples (column 2) or with POP (column 3)	n = 31/136 (22.8%)	n = 24/168 (14.3%)
No. bacterial species isolated from QEBA samples (column 2) or from PSB or PTC (column 3)	n = 39	n = 29
Haemophilus	19/31 (61.3%)	10/24 (41.7%)	NS
β-Lactamase positive	5/19 (26.3%)	4/10 (40%)	NS
Streptococcus pneumoniae	9/31 (29.0%)	6/24 (25%)	NS
MIC peni G ⩾ 0.125	2/9 (22.2%)	6/6 (100%)	NS
Other Streptococcus	3/31 (9.7%)	3/24 (12.5%)	NS
Staphylococcus aureus	2/31 (12.5%)	1/24 (4.2%)	NS
Gram-negative bacteria^*	6/31 (193%)	9/24 (37.5%)	NS
Pseudomonas species	1/31 (3.2%)	6/24 (25%)	NS (p = 0.06)
Enterobacter species	3/31 (9.7%)	2/24 (8.7%)	NS
Serratia species	1/31 (3.2%)	3/24 (12.5%)	NS
Morganella species	1/31 (3.2%)	0/24 (0.0%)	NS
Resistant gram negative^†	5/6 (83.3%)	7/10 (70%)	NS
Polymicrobial POP	9/31 (29.0%)	8/24 (33.3%)	NS

Definition of abbreviations: MIC peni G = minimal inhibitory concentration for penicillin G; NS = not significant; PSB = protected specimen brush; PTC = plugged telescopic catheter sample; QEBA = quantitative endobronchial aspirate.

^* Other than Haemophilus.

^† Resistant gram negative: strains with diminished sensitivity to standard targeted antibiotics (resistance R ⩾ 1 as defined: Pseudomonas species [R0, ticarcillin sensitive; R1, ticarcillin intermediate or resistant and ceftazidime sensitive; R2, ceftriaxone intermediate or resistant]; enterobacteria [R0, penicillin G sensitive; R1, ticarcillin intermediate or resistant and ceftazidime sensitive; R2, ceftriaxone intermediate or resistant]).

^‡ p < 0.05.

^§ p ⩾ 0.05 (NS). Yates correction applied when appropriate.

In 24 of 31 (77.4%) cases, a concordance was observed for at least one germ between the two sides. In 20 of 31 (64.5%) patients, the concordance between the two sides was strict (the same germs were found on both sides), even in the three patients in whom two germs were found on each side. Among these 20 patients, the level of colonization (in terms of colony-forming units) was identical in 14 of 20 cases (70%). In 4 of 31 patients, the concordance was not strict (an identical germ on both sides plus another germ in one of the sides). In 7 of 31 cases, germs were found in only one side (without predominance with respect to the operated side).

In the first 30 cases of the series, a protected distal specimen was obtained from the resected lung. In all these cases, no germ could be cultured (no growth observed), in spite of the isolation of predominant bacteria at bronchial aspiration in seven cases. Thus, the practice of systematic protected distal sampling was discontinued.

The incidence of POP was 25% (42 of 168). Documented and nondocumented POP were recorded in 24 (14.3%) and 18 (10.7%) cases, respectively. Among patients with nondocumented POP, culture of plugged telescopic catheter or protected specimen brush sample was completely negative in 16 of 18 cases and bacterial growth below the defined threshold was observed in two cases.

Other thoracic infections and requirement for postoperative antibiotherapy are detailed in Table 5.

TABLE 5. **POSTOPERATIVE INFECTIONS**
Infection Type and Treatment	No. (%) of Patients^*
Type of infection
Total POP, no. (%)	42 (25)
Documented POP, no. (%)	24 (14.3)
Nondocumented POP, no. (%)	18 (10.7)
Acute bronchitis, no. (%)	9 (5.3)
Wound infections, no. (%)	5 (2.9)^†
Empyemas without fistula, no. (%)	8 (4.7)
Treatment
Antibiotics, no. (%)	70 (41.6)
Antibiotherapy for thoracic infections, no. (%)	63 (37.5)
Antibiotherapy for other causes, no. (%)	7 (4.2)

Definition of abbreviation: POP = postoperative pneumonia.

^* Total number of patients surveyed: 168.

^† Only four of five wound infections necessitated antibiotherapy.

POP (both documented and nondocumented) occurred primarily during the first postoperative week (35 of 42, 83.3%; Figure 1A), with half of cases occurring by Postoperative Day 4.

Figure 1. (A) Occurrence of documented and nondocumented postoperative pneumonia (POP) with respect to postoperative day. (B) Pathogenic strains isolated from documented POP with respect to operative day. (C) Number of documented POP in colonized or noncolonized patients according to the time elapsed after surgery. X-axis numbers indicate postoperative period in days.

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Haemophilus, Streptococcus sp, Pseudomonas, and Serratia species were the predominant pathogens responsible for POP (respectively: 41.7, 37.5, 25, and 12.5%). In 33.3% of documented POP (8 of 24), more than one pathogen was documented (Table 4, column 2). All the S. pneumoniae strains (6 of 6) had decreased sensitivity to penicillin G (MIC ⩾ 0.06 mg/L) and four of 10 Haemophilus isolates were β-lactamase positive. Seven of 10 gram-negative bacteria other than Haemophilus species had decreased sensitivity to standard targeted antibiotics (for definition, see Table 4). A comparison between bacteria isolated in documented POP and those cultured on intraoperative bronchial aspiration is shown in Table 4.

Among the 31 colonized patients, 15 (48.4%) had POP (documented in 9 cases), whereas among noncolonized patients, POP occurred in 20 of 105 cases (19.0%, p = 0.004; relative risk, 3.84). The remaining seven cases of POP occurred in patients who did not receive intraoperative bronchial aspiration (n = 32). Among the nine patients with positive intraoperative aspirates (colonized patients) who developed documented POP, a concordance between the pathogen responsible for colonization and POP could be proven in six cases (85%; in two of them POP was due to two pathogens, the germ responsible for colonization and another one). The only POP related to a pathogen different from the one isolated by operative bronchial sampling occurred late in the postoperative period (Postoperative Day 11).

The different germs recovered from POP are plotted against time in Figure 1B. Streptococcus species and S. pneumoniae were recovered in all cases by Postoperative Day 6. POP occurred earlier among colonized patients than among noncolonized patients (mean days, 3.5 ± 2.7 vs. 6.7 ± 4.2; p = 0.023). Figure 1C shows the time when pathogens were isolated from fiberoptic samples in either colonized and noncolonized patients developing POP. Among the 12 pathogens responsible for POP occurring by Postoperative Day 4, 10 (83.3%) were isolated from colonized patients, with a peak on Postoperative Day 1 (5 of 6).

No relationship was observed between the level of colonization (10⁴, 10⁵, and 10⁶ cfu/ml) and the occurrence of POP.

Overall operative mortality observed during the study period was 6.5% (11 of 168). POP represented the cause of death for 8 of 11 patients. On the other hand, among patients who developed POP, the mortality rate was 19% (8 of 42), whereas the mortality rate was 2.4% among patients who did not develop POP (p = 0.00123). Mortality rates among colonized and noncolonized patients were 11.1% (3 of 27) and 4.6% (5 of 109). This difference did not reach statistical significance (p = 0.29; Table 6).

TABLE 6. **MAIN OUTCOME PARAMETERS FOR PATIENTS WITH OR WITHOUT POSTOPERATIVE PNEUMONIA**
	Overall	With POP	Without POP
	(n = 168)	(n = 42)	(n = 126)	p Value
Noninvasive ventilation, no. (%)	26 (15.5)	19 (45.2)	7 (5.6)	< 0.0000001
Reintubation,^* no. (%)	15 (9.0)	10 (23.8)	5 (4.0)	0.00075
Median ICU stay (d), mean (range)	4 (2–7)	7 (5–13)	3 (2–5)	< 0.0000001
OMEGA score,^† mean ± SD	172 ± 246	350 ± 387	109 ± 116	< 0.0000001
Median hospital stay (d), mean (range)	10 (8–14)	16 (11–22)	9 (7–12)	0.0000005
30-d mortality, no. (%)	11 (6.5)	8 (19.0)	3 (2.4)	0.00123

Definition of abbreviations: ICU = intensive care unit; POP = postoperative pneumonia.

^* Reintubation means late postoperative mechanical ventilation. After surgery, all the patients had been successfully extubated in the recovery room within 6 h of the end of surgery.

^† OMEGA = therapeutic intensity score for patients in an intensive care unit (57, 58).

Patients with POP required noninvasive ventilation or reintubation more frequently than did patients who did not develop POP (p < 0.0000001 and p = 0.00075, respectively). POP was associated with longer ICU and total hospital stay (p < 0.0000001 and p = 0.0000005, respectively). The OMEGA score was increased in patients with POP (p < 0.0000001; Table 6).

The following risk factors for the development of POP were identified on univariate analysis (Table 7): smoking history, underlying COPD (stage II, defined according to Pauwels and coworkers [59]), FEV₁ less than 80% of the predicted value, male sex, alcohol consumption, intraoperative bronchial colonization, type of resection (lobectomy), previous thoracotomy, and preoperative chemotherapy.

TABLE 7. **RISK FACTORS FOR POSTOPERATIVE PNEUMONIA AMONG PATIENTS UNDERGOING MAJOR LUNG RESECTION FOR NONINFECTIOUS DISEASES AND NOT CLINICALLY INFECTED AT THE TIME OF SURGERY**
	Odds Ratio (95% Confidence Limit)	p Value
Univariate analysis
Age > 70 yr	0.81 (0.33–1.96)	NS
Sex (M/F)^*	11.2 (2.16–58.5)	p = 0.004
Karnofsky ⩽ 80	1.40 (0.85–2.28)	NS
NSCLC/metastasis	2.42 (0.31–19.1)	NS
POP risk score ⩾ 40	2.24 (0.89–5.61)	NS
Body mass index ⩾ 25	0.55 (0.25–1.2)	NS
Weight loss ⩾ 10%	1.65 (0.65–4.2)	NS
Smoking history	9.43 (1.73–51.53)	p = 0.0096
Smoking cessation ⩽ 60 d	2.01 (0.94–4.28)	NS (p = 0.07)
Alcohol consumption	3.1 (1.37–7.0)	p = 0.0066
FEV₁ (% predicted) ⩽ 80%	2.47 (1.18–5.19)	p = 0.016
COPD
Stage 0 (at risk)	1.56 (0.83–2.94)	NS
Stage I (mild COPD)	1.27 (0.52–3.1)	NS
Stage II (moderate COPD)	2.46 (1.45–4.17)	p = 0.00087
Stage III (severe COPD)	ND	ND
Diabetes mellitus	0.53 (0.15–1.80)	NS
Chronic renal insufficiency	0.73 (0.08–6.7)	NS
Preoperative chemotherapy	0.32 (0.11–0.93)	p = 0.037
Previous radiotherapy	0.41 (0.05–3.2)	NS
Previous head and neck surgery	3.05 (0.21–43.6)	NS
ASA (III–IV/I–II)	1.58 (0.77–3.28)	NS
Preoperative CRP ⩾ 20 mg/ml	0.45 (0.17–1.25)	NS
Intraoperative bronchial colonization	3.84 (1.47–7.61)	p = 0.004
Side of resection (right/left)	0.80 (0.39–1.61)	NS
Lobectomy/pneumonectomy	3.43 (1.19–9.86)	p = 0.022
Sleeve resection	2.55 (0.68–9.6)	NS
Chest wall resection	0.41 (0.05–3.2)	NS
Previous thoracotomy	0.15 (0.02–0.87)	p = 0.04
Procedure time	0.97 (0.88–1.2)	NS
NIV before POP	1.99 (0.95–4.15)	NS
Multivariate analysis^*
Lobectomy/pneumonectomy	8.92 (1.97–40.4)	p = 0.00077
Moderate COPD	4.88 (1.71–13.86)	p = 0.0026
Sex (M/F)	7.18 (0.88–58.0)	p = 0.02
Intraoperative bronchial colonization	3.6 (1.09–12.25)	p = 0.033

Definition of abbreviations: ASA = American Society of Anesthesiology score; COPD = chronic obstructive pulmonary disease; CRP = C-reactive protein; ND = not determined; NIV = noninvasive ventilation; NS = not significant; NSCLC = non–small cell lung cancer; POP = postoperative pneumonia.

^* All variables were included in the multivariate regression analysis. Global p value of the model: p = 0.0000011.

Multivariate analysis showed that the presence of underlying COPD (stage II), the type of resection (lobectomy or bilobectomy vs. pneumonectomy), intraoperative bronchial colonization, and male sex (Table 7) were independent risk factors for the development of POP.

DISCUSSION

Section:

In this prospective study including 168 patients undergoing major lung resection for noninfectious diseases, POP occurred in 42 of them (25%). Mortality from POP was as high as 19% and POP represented the leading cause of mortality (8 of 11 deaths).

Comparison with previously published data on the topic is difficult as the subject has been relatively poorly studied. Few surgical series have specifically targeted the problem of POP after lung resection, as in most instances the relative contribution of POP to the overall mortality is not stated, and data about the incidence and characteristics of POP are poor.

Few studies performed so far provide sufficient information about the incidence, the clinical characteristics, the microbiological point of view, and the outcome of POP in thoracic surgery (Tables 1 and 2). In two prospective studies, both dealing with more than 100,000 patients undergoing different types of surgery, Arozullah and coworkers showed that POP was particularly frequent in general thoracic surgery (4) and was associated with a particularly high risk of death (5). Unfortunately, all types of thoracic surgical procedure were included in these studies.

Extreme variability in terms of incidence of POP after lung resection is reported in both retrospective and prospective studies, with values ranging from 2 to 40%. Such variability probably depends on the characteristics of studied populations, the type of surgical resection, antibioprophylaxis, and postoperative management. Furthermore, as stated above, the criteria for defining POP and the methods for their identification are extremely variable.

In our experience, a high incidence of POP (25%) was observed. Twenty-four of 42 cases of POP (57%) could be microbiologically proven with cultures of samples obtained at fiberoptic bronchoscopy. This percentage of documentation is similar to that reported in series dealing with community-acquired pneumonias (50–70%) (60) or with pneumonia in patients with lung cancer under medical treatment (61%) (61).

In our series, most POP occurred in the early postoperative week. This early incidence of POP after thoracic surgery is in agreement with a previously published study (62). The documented kinetics of POP are probably related to antibioprophylaxis: on Postoperative Day 2 (immediately after the end of antibioprophylaxis), no POP could be microbiologically documented, whereas during subsequent days the documented percentage progressively increased to reach a plateau at 80%. On Postoperative Day 1, the documented percentage was relatively elevated (56%), while antibiotic prophylaxis was still ongoing: this phenomenon can be probably explained by the fact that these POP occurred in almost all instances among colonized patients, and the inoculum was probably particularly high. Furthermore, the bacteria responsible often had a reduced sensitivity to cefamandol.

In our series, pathogenic bacteria were in most instances those classically reported for early hospital-acquired pneumonia: H. influenzae (41.7%), S. pneumoniae (25%), and other streptococci (12.5%) (62). Enterobacter and Pseudomonas species were responsible for 8.7 and 25% of cases, respectively. A polymicrobial etiology was recognized in 33.3% of patients. In the few previous studies performed so far to assess microbiological characteristics of POP, results were somewhat similar. Bernard and coworkers (1) found that Streptococcus species and H. influenzae were responsible for 50% of all POP, whereas gram-negative pathogens (other than Haemophilus species) accounted for 31% of pneumonias. In the experience of Sok and coworkers (7), gram-negative pathogens (other than Haemophilus species) were responsible for 71% of POP and Streptococcus species were found in only 10% of cases. Unfortunately, in this last study, single-dose cefuroxime was used as preoperative antibioprophylaxis, but 44% of patients had been treated with the same drug for 1–6 d preoperatively, with a possible impact on their bacterial flora.

In our study, culture of intraoperative bronchial aspiration showed that 22.2% of S. pneumoniae strains had decreased sensitivity to penicillin G and 5 of 19 (26.3%) Haemophilus strains were β-lactamase positive, these last figures being in agreement with available data on resistance in the setting of both community-acquired respiratory infection (63) and of medically treated lung cancer (61).

On the other hand, all S. pneumoniae strains isolated from patients with POP (6 of 6) had decreased sensitivity to penicillin G, whereas four of nine (44.4%) Haemophilus isolates were β-lactamase positive. Furthermore, 6 of 10 gram-negative bacteria other than Haemophilus species had diminished sensitivity to standard targeted antibiotics.

The possibility that colonization should be considered as a predisposing factor for POP is further strengthened by other arguments. POP developed more frequently in colonized patients than in noncolonized patients (44.4 vs. 21%, p = 0.004). Furthermore, POP in colonized patients occurred earlier in the postoperative period. Among patients colonized with S. pneumoniae, none of those with a fully sensitive strain developed POP, whereas this last occurred frequently among patients with strains characterized by reduced sensitivity to penicillin G. Our hypothesis is that cefamandol prophylaxis may prevent POP sustained by S. pneumoniae with normal sensitivity to β-lactamines. Multivariate analysis could identify colonization as a predisposing factor to POP together with COPD (stage II), male sex, and the extent of resection (lobectomy being associated with a higher risk). In the series by Arozullah and coworkers, all these factors (4) (with the exception of the kind of pulmonary exeresis, the series dealing with all types of surgical procedure) were recognized as independent risk factors for POP, thus suggesting that individual risk factors would play a major role in the pathogenesis of POP, regardless of the type of surgery.

Our results show that POP after major lung resection is frequent, severe, and precocious. Germs typically responsible for community-acquired pneumonia (64) and classically isolated from patients with COPD (27, 58, 65) are often responsible for these instances of POP. Pathogens cultured from intraoperative bronchial samples are likely to be responsible for a significant percentage of POP, but the antibioprophylaxis based on a second-generation cephalosporin is in several instances not optimal. Although antibioprophylaxis with a second-generation cephalosporin is usually effective in the prevention of wound infection and empyema, it does not specifically target the respiratory pathogens found in these patients. A more adapted prophylaxis might be able to decrease the rate of in-hospital acquired pneumonia after thoracic surgery and should be evaluated.

References

Section:

1.	Bernard AC, Deschamps C, Allen MS, Miller DL, Trastek VF, Jenkins GD, Pairolero PC. Pneumonectomy for malignant disease: factors affecting early morbidity and mortality. J Thorac Cardiovasc Surg 2001;121:1076–1082. Crossref, Medline, Google Scholar
2.	Watanabe S, Asamura H, Suzuki K, Tsuchiya R. Recent results of postoperative mortality for surgical resections in lung cancer. Ann Thorac Surg 2004;78:999–1002 [discussion 1002–1003]. Crossref, Medline, Google Scholar
3.	Wada HT, Nakamura N, Nakamoto K, Maeda M, Watanabe Y. Thirty-day operative mortality for thoracotomy in lung cancer. J Thorac Cardiovasc Surg 1998;115:70–73. Crossref, Medline, Google Scholar
4.	Arozullah AM, Khuri SF, Henderson WG, Daley J. Development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery. Ann Intern Med 2001;135:847–857. Crossref, Medline, Google Scholar
5.	Arozullah AM, Henderson WG, Khuri SF, Daley J. Postoperative mortality and pulmonary complication rankings: how well do they correlate at the hospital level? Med Care 2003;41:979–991. Crossref, Medline, Google Scholar
6.	Ferdinand B, Shennib H. Postoperative pneumonia. Chest Surg Clin N Am 1998;8:529–539. Medline, Google Scholar
7.	Sok M, Dragas AZ, Erzen J, Jerman J. Sources of pathogens causing pleuropulmonary infections after lung cancer resection. Eur J Cardiothorac Surg 2002;22:23–27 [discussion 27]. Crossref, Medline, Google Scholar
8.	Boldt J, Piper S, Uphus D, Fussle R, Hempelmann G. Preoperative microbiologic screening and antibiotic prophylaxis in pulmonary resection operations. Ann Thorac Surg 1999;68:208–211. Crossref, Medline, Google Scholar
9.	Ioanas M, Angrill J, Baldo X, Arancibia F, Gonzalez J, Bauer T, Canalis E, Torres A. Bronchial bacterial colonization in patients with resectable lung carcinoma. Eur Respir J 2000;19:326–332. Google Scholar
10.	Wansbrough-Jones MH, Nelson A, New L, Wilson A, Wright N, Pepper JR. Bronchoalveolar lavage in the prediction of post-thoracotomy chest infection. Eur J Cardiothorac Surg 1991;5:433–434 [discussion 435]. Crossref, Medline, Google Scholar
11.	Tarkka M, Pokela R, Lepojarvi M, Nissinen J, Karkola P. Infection prophylaxis in pulmonary surgery: a randomized prospective study. Ann Thorac Surg 1987;44:508–513. Crossref, Medline, Google Scholar
12.	Algar FJ, Alvarez A, Salvatierra A, Baamonde C, Aranda JL, Lopez-Pujol FJ. Predicting pulmonary complications after pneumonectomy for lung cancer. Eur J Cardiothorac Surg 2003;23:201–208. Crossref, Medline, Google Scholar
13.	Ploeg AJ, Kappetein AP, van Tongeren RB, Pahlplatz PV, Kastelein GW, Breslau PJ. Factors associated with perioperative complications and long-term results after pulmonary resection for primary carcinoma of the lung. Eur J Cardiothorac Surg 2003;23:26–29. Crossref, Medline, Google Scholar
14.	Jones DR, Stiles BM, Denlinger CE, Antippa P, Daniel TM. Pulmonary segmentectomy: results and complications. Ann Thorac Surg 2003;76:343–348 [discussion 348–349]. Crossref, Medline, Google Scholar
15.	Hollaus PH, Wilfing G, Wurnig PN, Pridun NS. Risk factors for the development of postoperative complications after bronchial sleeve resection for malignancy: a univariate and multivariate analysis. Ann Thorac Surg 2003;75:966–972. Crossref, Medline, Google Scholar
16.	Stamatis G, Djuric D, Eberhardt W, Pottken C, Zaboura G, Fechner S, Fujimoto T. Postoperative morbidity and mortality after induction chemoradiotherapy for locally advanced lung cancer: an analysis of 350 operated patients. Eur J Cardiothorac Surg 2002;22:292–297. Crossref, Medline, Google Scholar
17.	Vaporciyan AA, Merriman KW, Ece F, Roth JA, Smythe WR, Swisher SG, Walsh GL, Nesbitt JC, Putnam JB. Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation. Ann Thorac Surg 2002;73:420–425 [discussion 425–426]. Crossref, Medline, Google Scholar
18.	Doddoli C, Thomas P, Thirion X, Seree Y, Giudicelli R, Fuentes P. Postoperative complications in relation with induction therapy for lung cancer. Eur J Cardiothorac Surg 2001;20:385–390. Crossref, Medline, Google Scholar
19.	Siegenthaler MP, Pisters KM, Merriman KW, Roth JA, Swisher SG, Walsh GL, Vaporciyan AA, Smythe WR, Putnam JB. Preoperative chemotherapy for lung cancer does not increase surgical morbidity. Ann Thorac Surg 2001;71:1105–1111 [discussion 1111–1112]. Crossref, Medline, Google Scholar
20.	Uramoto H, Nakanishi R, Fujino Y, Imoto H, Takenoyama M, Yoshimatsu T, Oyama T, Osaki T, Yasumoto K. Prediction of pulmonary complications after a lobectomy in patients with non-small cell lung cancer. Thorax 2001;56:59–61. Crossref, Medline, Google Scholar
21.	Stephan F, Boucheseiche S, Hollande J, Flahault A, Cheffi A, Bazelly B, Bonnet F. Pulmonary complications following lung resection: a comprehensive analysis of incidence and possible risk factors. Chest 2000;118:1263–1270. Crossref, Medline, Google Scholar
22.	Hubaut JJ, Baron O, Al Habash O, Despins P, Duveau D, Michaud JL. Closure of the bronchial stump by manual suture and incidence of bronchopleural fistula in a series of 209 pneumonectomies for lung cancer. Eur J Cardiothorac Surg 1999;16:418–423. Crossref, Medline, Google Scholar
23.	Aoki T, Yamato Y, Tsuchida M, Watanabe T, Hayashi J, Hirono T. Pulmonary complications after surgical treatment of lung cancer in octogenarians. Eur J Cardiothorac Surg 2000;18:662–665. Crossref, Medline, Google Scholar
24.	Mitchell JD, Mathisen DJ, Wright CD, Wain JC, Donahue DM, Moncure AC, Grillo HC. Clinical experience with carinal resection. J Thorac Cardiovasc Surg 1999;117:39–52 [discussion 52–53]. Crossref, Medline, Google Scholar
25.	Yano T, Yokoyama H, Fukuyama Y, Takai E, Mizutani K, Ichinose Y. The current status of postoperative complications and risk factors after a pulmonary resection for primary lung cancer: a multivariate analysis. Eur J Cardiothorac Surg 1997;11:445–449. Crossref, Medline, Google Scholar
26.	Busch E, Verazin G, Antkowiak JG, Driscoll D, Takita H. Pulmonary complications in patients undergoing thoracotomy for lung carcinoma. Chest 1994;105:760–766. Crossref, Medline, Google Scholar
27.	Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002;57:759–764. Crossref, Medline, Google Scholar
28.	Tedder M, Anstadt MP, Tedder SD, Lowe JE. Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy. Ann Thorac Surg 1992;54:387–391. Crossref, Medline, Google Scholar
29.	Wahi R, McMurtrey MJ, DeCaro LF, Mountain CF, Ali MK, Smith TL, Roth JA. Determinants of perioperative morbidity and mortality after pneumonectomy. Ann Thorac Surg 1989;48:33–37. Crossref, Medline, Google Scholar
30.	Keagy BA, Lores ME, Starek PJ, Murray GF, Lucas CL, Wilcox BR. Elective pulmonary lobectomy: factors associated with morbidity and operative mortality. Ann Thorac Surg 1985;40:349–352. Crossref, Medline, Google Scholar
31.	Turna A, Kutlu CA, Ozalp T, Karamustafaoglu A, Mulazimoglu L, Bedirhan MA. Antibiotic prophylaxis in elective thoracic surgery: cefuroxime versus cefepime. Thorac Cardiovasc Surg 2003;51:84–88. Crossref, Medline, Google Scholar
32.	Bonde P, McManus K, McAnespie M, McGuigan J. Lung surgery: identifying the subgroup at risk for sputum retention. Eur J Cardiothorac Surg 2002;22:18–22. Crossref, Medline, Google Scholar
33.	Jagoe RT, Goodship TH, Gibson GJ. The influence of nutritional status on complications after operations for lung cancer. Ann Thorac Surg 2001;71:936–943. Crossref, Medline, Google Scholar
34.	Beccaria M, Corsico A, Fulgoni P, Zoia MC, Casali L, Orlandoni G, Cerveri I. Lung cancer resection: the prediction of postsurgical outcomes should include long-term functional results. Chest 2001;120:37–42. Crossref, Medline, Google Scholar
35.	Bernard A, Ferrand L, Hagry O, Benoit L, Cheynel N, Favre JP. Identification of prognostic factors determining risk groups for lung resection. Ann Thorac Surg 2000;70:1161–1167. Crossref, Medline, Google Scholar
36.	Wang J, Olak J, Ultmann RE, Ferguson MK. Assessment of pulmonary complications after lung resection. Ann Thorac Surg 1999;67:1444–1447. Crossref, Medline, Google Scholar
37.	Ribas J, Diaz O, Barbera JA, Mateu M, Canalis E, Jover L, Roca J, Rodriguez-Roisin R. Invasive exercise testing in the evaluation of patients at high-risk for lung resection. Eur Respir J 1998;12:1429–1435. Crossref, Medline, Google Scholar
38.	Melendez JA, Barrera R. Predictive respiratory complication quotient predicts pulmonary complications in thoracic surgical patients. Ann Thorac Surg 1998;66:220–224. Crossref, Medline, Google Scholar
39.	Duque JL, Ramos G, Castrodeza J, Cerezal J, Castanedo M, Yuste MG, Heras F; Grupo Cooperativo de Carcinoma Broncogenico de la Sociedad Espanola de Neumologia y Cirugia Toracica. Early complications in surgical treatment of lung cancer: a prospective, multicenter study. Ann Thorac Surg 1997;63:944–950. Crossref, Medline, Google Scholar
40.	Harpole DH, Liptay MJ, DeCamp MM, Mentzer SJ, Swanson SJ, Sugarbaker DJ. Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg 1996;61:977–982. Crossref, Medline, Google Scholar
41.	Deslauriers J, Ginsberg RJ, Piantadosi S, Fournier B. Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. Chest 1994;106:329S–330S. Crossref, Medline, Google Scholar
42.	Kearney DJ, Lee TH, Reilly JJ, DeCamp MM, Sugarbaker DJ. Assessment of operative risk in patients undergoing lung resection: importance of predicted pulmonary function. Chest 1994;105:753–759. Crossref, Medline, Google Scholar
43.	Bernard A, Pillet M, Goudet P, Viard H. Antibiotic prophylaxis in pulmonary surgery: a prospective randomized double-blind trial of flash cefuroxime versus forty-eight–hour cefuroxime. J Thorac Cardiovasc Surg 1994;107:896–900. Crossref, Medline, Google Scholar
44.	Dales RE, Dionne G, Leech JA, Lunau M, Schweitzer I. Preoperative prediction of pulmonary complications following thoracic surgery. Chest 1993;104:155–159. Crossref, Medline, Google Scholar
45.	Wertzel H, Swoboda L, Joos-Wurtemberger A, Frank U, Hasse J. Perioperative antibiotic prophylaxis in general thoracic surgery. Thorac Cardiovasc Surg 1992;40:326–329. Crossref, Medline, Google Scholar
46.	Krasnik M, Thiis J, Frimodt-Moller N. Antibiotic prophylaxis in non-cardiac thoracic surgery: a double-blind study of penicillin vs. cefuroxime. Scand J Thorac Cardiovasc Surg 1991;25:73–76. Crossref, Medline, Google Scholar
47.	Olak J, Jeyasingham K, Forrester-Wood C, Hutter J, al-Zeerah M, Brown E. Randomized trial of one-dose versus six-dose cefazolin prophylaxis in elective general thoracic surgery. Ann Thorac Surg 1991;51:956–958. Crossref, Medline, Google Scholar
48.	Aznar R, Mateu M, Miro JM, Gatell JM, Gimferrer JM, Aznar E, Mallolas J, Soriano E, Sanchez-Lloret J. Antibiotic prophylaxis in non-cardiac thoracic surgery: cefazolin versus placebo. Eur J Cardiothorac Surg 1991;5:515–518. Crossref, Medline, Google Scholar
49.	Ilves R, Cooper JD, Todd TR, Pearson FG. Prospective, randomized, double-blind study using prophylactic cephalothin for major, elective, general thoracic operations. J Thorac Cardiovasc Surg 1981;81:813–817. Crossref, Medline, Google Scholar
50.	Frimodt-Moller N, Ostri P, Pedersen IK, Poulsen SR. Antibiotic prophylaxis in pulmonary surgery: a double-blind study of penicillin versus placebo. Ann Surg 1982;195:444–450. Crossref, Medline, Google Scholar
51.	Nan DN, Fernandez-Ayala M, Farinas-Alvarez C, Mons R, Ortega FJ, Gonzales-Macias J, Farinas C. Nosocomial infection after lung surgery: incidence and risk factors. Chest 2005;128:2647–2652. Crossref, Medline, Google Scholar
52.	Belda J, Cavalcanti M, Ferrer M, Serra M, Puid de la Bellacasa J, Canalis E, Torres A. Bronchial colonization and postoperative respiratory infections in patients undergoing lung cancer surgery. Chest 2005;128:1571–1579. Crossref, Medline, Google Scholar
53.	Bluman LG, Mosca L, Newman N, Simon DG. Preoperative smoking habits and postoperative pulmonary complications. Chest 1998;113:883–889. Crossref, Medline, Google Scholar
54.	Sekine Y, Behnia M, Fujisawa T. Impact of COPD on pulmonary complications and on long-term survival of patients undergoing surgery for NSCLC. Lung Cancer 2002;37:95–101. Crossref, Medline, Google Scholar
55.	Martin J, Ginsberg RJ, Abolhoda A, Bains MS, Downey RJ, Korst RJ, Weigel TL, Kris MG, Venkatraman ES, Rusch VW. Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy. Ann Thorac Surg 2001;72:1149–1154. Crossref, Medline, Google Scholar
56.	Roberts JR, Eustis C, Devore R, Carbone D, Choy H, Johnson D. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung cancer. Ann Thorac Surg 2001;72:885–888. Crossref, Medline, Google Scholar
57.	Montuclard L, Garrouste-Orgeas M, Timsit JF, Misset B, De Jonghe B, Carlet J. Outcome, functional autonomy, and quality of life of elderly patients with a long-term intensive care unit stay. Crit Care Med 2000;28:3389–3395. Crossref, Medline, Google Scholar
58.	Sznajder M, Leleu G, Buonamico G, Auvert B, Aegerter P, Merliere Y, Dutheil M, Guidet B, Le Gall JR. Estimation of direct cost and resource allocation in intensive care: correlation with Omega system. Intensive Care Med 1998;24:582–589. Crossref, Medline, Google Scholar
59.	Pauwels RA, Buist S, Calverley PMA, Jenkins CR, Hurd SZ; GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:1256–1276. Abstract, Medline, Google Scholar
60.	Rello J, Bodi M, Mariscal D, Navarro M, Diaz E, Gallego M, Valles J. Microbiological testing and outcome of patients with severe community acquired pneumonia. Chest 2003;123:174–180. Crossref, Medline, Google Scholar
61.	Berghmans T, Sculier JP, Klastersky J. A prospective study of infections in lung cancer patients admitted to the hospital. Chest 2003;124:114–120. Crossref, Medline, Google Scholar
62.	Frey DJ, Reichmann AK, Mauch H, Kaiser D. “Single-shot” antibiotic prophylaxis in thoracic surgery: reduction of the postoperative infection rate. Infection 1993;21:S35–S44. Crossref, Medline, Google Scholar
63.	Jacobs MR, Felmingham D, Appelbaum PC, Gruneberg RN. The Alexander Project 1998–2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J Antimicrob Chemother 2003;52:229–246. Crossref, Medline, Google Scholar
64.	American Thoracic Society. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies: a consensus statement. Am J Respir Crit Care Med 1996;153:1711–1725. Abstract, Medline, Google Scholar
65.	Cabello H, Torres A, Celis R, El-Ebiary M, Puig de la Bellacasa J, Xaubet A, Gonzalez J, Agusti C, Soler N. Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study. Eur Respir J 1997;10:1137–1144. Crossref, Medline, Google Scholar

Correspondence and requests for reprints should be addressed to M. Alifano, M.D., Unité de Chirurgie Thoracique, Hôpital Hôtel-Dieu, 1 Place Parvis de Nôtre Dame, 75004 Paris, France. E-mail: [email protected]

American Journal of Respiratory and Critical Care Medicine

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