Atelectasis

Objectives: To assess the ability of selective bronchography to predict which patients with neoplastic postobstructive atelectasis will respond to interventional therapies directed at the reexpansion of the affected lung. Furthermore, to compare the utility of selective bronchography with the current predictive standard that reversal of postobstructive atelectasis is unlikely when it is [greater than or equal to] 4 weeks in duration (ie, the 4-week rule).

Design: A prospective observational study.

Setting: A tertiary care referral center/medical school.

Patients: Twenty-seven consecutive patients with advanced lung cancer or other malignancy, with documented neoplastic postobstructive atelectasis involving a total of 44 lobes.

Interventions: Lobar collapse was documented radiographically. The duration of atelectasis was investigated and quantified as accurately as possible. Prior to the use of interventional therapies, selective bronchography was performed on each collapsed lobe, and the results were documented. Bronchography results did not influence the decision to proceed with interventional therapies. Patients had each of their collapsed lobes manipulated by interventional techniques that were directed at reexpansion of the lung. One week after the patient underwent the intervention, the degree of reexpansion was assessed radiographically.

Results: Interventional therapies leading to significant reversal of airway narrowing were completed in all 44 lobes. These were successful in reexpanding 28 of 44 collapsed lobes (64%). Selective bronchography demonstrated the following two distinct patterns: an intact bronchial tree (ie, tree pattern); or the absence of a distinguishable, distal bronchial tree (ie, blush pattern). The sensitivity of selective bronchography to predict reexpansion is 1.00 (95% confidence interval [CI], 0.90 to 1.00), and its specificity is 0.56 (95% CI, 0.30 to 0.80). There were no complications attributable to selective bronchography. The sensitivity of the 4-week rule to predict reexpansion is 0.61 (95% CI, 0.41 to 0.78), and its specificity is 0.75 (95% CI, 0.48 to 0.93). The results of selective bronchography and use of the 4-week rule were significantly different in predicting which lobes would reexpand and which would not (p = 0.0026). Using selective bronchography to predict the reversal of lobar atelectasis, the positive predictive value of the tree pattern was 0.80 and the negative predictive value of the blush pattern was 1.00. The values for the 4-week rule are 0.81 and 0.52, respectively.

Conclusions: Selective bronchography is a useful tool for predicting whether patients with neoplastic postobstructive atelectasis would benefit from interventional techniques that are directed at lobar reexpansion. Selective bronchography appears to be superior to the 4-week rule in this regard.

(CHEST 2003; 123:828-834)

Key words: airway obstruction; atelectasis; bronchography; bronchoscopy; etiology; lung neoplasm; radiography; surgery

Abbreviation: CI = confidence interval

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Lung cancer is a widespread disease that accounts for the majority of cancer deaths worldwide. Large portions of new lung cancer cases are diagnosed in an advanced stage, at which time curative surgery is not an option. (1) These patients often have endobronchial tumors, causing significant morbidity in the form of debilitating wheezing, cough, hemoptysis, dyspnea, and postobstructive pathophysiology. Postobstructive pathophysiology can lead to debilitation and poor performance status from worsening hypoxemia, atelectasis, and postobstructive pneumonia. Many of these patients have chemotherapy and/or radiation therapy regimens discontinued or delayed due to poor performance status. As a result, a common approach to the preservation of function in these patients is the restoration of airflow into obstructed portions of the lung.

The treatment options for bronchial narrowing due to neoplasm include standard chemotherapy, radiation therapy, and bronchoscopic interventional procedures. The ability to ablate the intraluminal tumor has been examined in multiple retrospective analyses, (1-7) and it has been suggested that direct tumor destruction with restoration of the airway lumen from interventional procedures is a superior local ablative technique to both chemotherapy and external beam radiation therapy. Direct tumor destruction with luminal restoration can be accomplished using a variety of methods such as Nd-YAG laser therapy, cryotherapy, electrocautery, brachytherapy, photodynamic therapy, and balloon dilatation with stent placement. (8-10) These techniques, whether used alone or in combination, collectively form the armamentarium of interventional pulmonology and are distinct from standard diagnostic bronchoscopic procedures. As well as being labor-intensive and cost-intensive, these interventions convey some risks in addition to the promise of benefit.

To optimize patient well-being and the cost-effectiveness of their care, a reliable predictor of benefit from interventional procedures that are aimed at reversing obstruction is needed, a reliable tool for prediction would decrease unwarranted interventions and, therefore, cost. The clinical guidelines usually employed for predicting a response to neoplastic postobstructive intervention are as follows: duration of collapse is > 4 weeks; and/or there is no visible airway beyond the neoplastic obstructions However, identifying patients who meet the 4-week criteria can be unreliable because there are seldom definitive symptoms or chest radiographs that can pinpoint duration of collapse. The 4-week rule has not been studied in randomized clinical trials and is recommended on the basis of expert opinion rather than evidence-based data.

Historically, bronchography has long been used to assess the anatomy and patency of the entire bronchial tree. (11) It has been classically performed by passing a catheter into the trachea, by means of which dry radiopaque contrast medium was instilled. The procedure is well-known to cause significant patient discomfort. Bronchospasm may be a serious complication related to this technique. (11) More advanced radiologic procedures, such as CT scanning and MRI, have replaced bronchography for airway visualization. Selective bronchography now serves as an adjunct to fiberoptic bronchoscopy, permitting the fluoroscopic assessment of portions of the lung that are beyond the reach of direct inspection. Newer contrast materials have essentially eliminated side effects and patient discomfort. (11,12)

Selective bronchography, used to optimize the patient's benefit from the application of interventional pulmonology techniques, has been relied on extensively in our program. An analysis of prospectively collected clinical data has suggested that selective bronchography may be used to improve the pretreatment predictive accuracy of the ability of interventional therapies to reexpand the atelectatic lung caused by neoplasm. Results comparing findings from selective bronchography with those of the 4-week rule and actual clinical outcomes are reported.

MATERIALS AND METHODS

Patients

Twenty-seven consecutive patients with neoplastic postobstructive atelectasis due to advanced-stage lung cancer or cancer metastatic to the lung were referred for interventional pulmonology therapy that was aimed at reexpanding the collapsed lobes. All patients had been offered chemotherapy and/or radiation therapy by an oncologist before referral. All patients had atelectasis confirmed by chest radiograph or CT scan. All patients had been tobacco abusers, however, smoking status at the time of intervention was not obtained. The duration of lobar collapse was estimated by a review of serial radiographs or by the determination of the onset of worsening dyspnea.

Selective Bronchography

Selective bronchography was performed at each airway site where interventional therapies were being considered. The information obtained from these images was used to guide decisions about which procedure would be employed. The reexpansion of the atelectatic lung was attempted at each site, independent of selective bronchography findings.

Selective bronchography was performed using a modified version of the procedure described by Koval et al. (11) Under combined bronchoscopic and fluoroscopic visualization, a guide-wire (Jagwire; Boston Scientific; Watertown, MA) was guided into the lung beyond the site of airway narrowing. Then, either a balloon catheter (Microvasive; Boston Scientific) or a contrast catheter (Olympus; Melville, NY) was threaded over the guide-wire. The guidewire was removed. Aliquots of a mixture of equal volumes of saline solution and meglumine (Hypaque; Nycomed; Princeton, NJ), to a maximum of 8 mL, were injected with constant manual pressure during continuous fluoroscopic visualization. The object of the procedure was first to confirm free, forward passage of the contrast medium then to opacify the distal structures. Each atelectatic lobe was studied independently, and its bronchographic appearance was documented prior to the performance of any other intervention. The interpretation of the lobar pattern seen with selective bronchography was a consensus agreement of the two interventional pulmonologist who were observing the real-time images. Only bronchograms without a trace of intact bronchial trees at anytime during the injection of contrast were determined to be blush patterns.

Interventional Pulmonology and Follow-up

After performing selective bronchography, the bronchial obstruction was reversed using tumor ablation and/or stenting techniques. Ablative techniques included the following: brachytherapy; cryotherapy; electrocautery; and photodynamic therapy. Stenting techniques included both balloon dilatation and self-expandable metal stent placement. The specific therapy, or combination of therapies, that was used was determined on a case-by-case basis with patient characteristics, amount of tumor burden, and location of the tumor being the primary considerations. Every atelectatic lobe that was studied by selective bronchography was manipulated by interventional techniques to attempt lung reexpansion regardless of the selective bronehogram appearance. Intervention was aimed at bypassing the initial airway obstruction, whether it was an extrinsic compression endobronchial growth or a mixture of both processes, and if this intervention was successful, we termed it reversal of airway narrowing.

The primary goal of treatment was to achieve resolution of atelectasis 1 week after interventional therapy based on findings from either a chest radiograph or CT scan. The 1-week end point was chosen for the following two reasons: first, to allow ample time for the clearance of trapped secretions after the obstruction was at least partially reversed; and, second, to keep the intervention to a short enough time that treatment with chemotherapy and/or radiation was not delayed.

Data Collection and Protection of Human Subjects

All data used in this report were prospectively collected in existing databases that were maintained in accordance with institutional patient care, quality assurance policies. The use of these data for this investigational purpose was reviewed and approved by the university and medical center institutional review board.

Statistical Analysis

Sensitivity, specificity, and positive and negative predictive values were calculated using standard statistical methods. The confidence intervals (CIs) for sensitivity and specificity were calculated by inverting the exact test for proportions based on the binomial distribution. When the sensitivity was estimated at 1.00, CIs represent a one-sided statistic. All other CIs are based on two-sided statistics. The statistical comparison between selective bronchography and the 4-week rule to reliably predict which lobes would reexpand was performed using the exact version of the McNemar binomial test. (13)

RESULTS

Twenty-seven patients (15 men and 12 women) were studied. One had endobronchial metastatic breast carcinoma, and all the rest had non-small cell lung cancer (at least stage IIIA). The mean duration of lobar collapse prior to interventional pulmonology was 6.8 weeks (range, 1 to 24 weeks). A total of 44 collapsed lobes were identified, evaluated, and treated (Table 1).

As we gained experience with selective bronchography, it became evident that only two easily distinguished anatomic patterns would be seen. One image was of an intact bronchial tree with varying degrees of dilation, termed the tree pattern (Fig. 1). Alternatively, the blush pattern did not show an intact bronchial tree distal to the obstruction (Fig. 2). Of the 44 selective bronchograms that were performed, 35 demonstrated tree patterns, and the remaining 9 demonstrated blush patterns. The average duration of collapse was 6.2 weeks for lobes having a tree bronchograms and 6.6 weeks for lobes having blush bronchograms.

[FIGURE 1-2 OMITTED]

Interventions reversed airway narrowing at the point of obstruction in all 44 lobes, which was confirmed by immediate postprocedure bronchoscopic inspection of the site and was documented by still photography. During the next week, the patients received only preprocedure medications, with the exception of bronchodilators, if they had not previously been part of their regimen. No patient received chemotherapy or radiation therapy as a new treatment during this week. One week post-procedure, there was radiographically evident reexpansion of 28 collapsed lobes (64%), all of which had a tree pattern seen on selective bronchography. Conversely, seven of the lobes showing a bronchographic tree pattern did not reexpand. None of nine lobes with a blush pattern were inflated a week after the intervention. These data are summarized graphically in Figure 3. There did not appear to be a pattern of more elaborate or in-depth interventions, depending on the duration of collapse, to account for the lesser number of lobes with tree pattern bronchograms that failed to have reversal of lobar collapse after 4 weeks than before.

[FIGURE 3 OMITTED]

The positive predictive value of reinflation of a lobe in which selective bronchography demonstrated a tree pattern was 0.80 (95% CI, 0.63 to 0.92), and the negative predictive value of the blush pattern was 1.00 (95% CI, 0.72 to 1.00), Using the distinction between the tree and blush patterns, the sensitivity of selective bronchography to predict the reexpansion of a lobe was 1.00 (95% CI, 0.90 to 1.00), and its specificity was 0.56 (95% CI, 0.30 to 0.80). No patients experienced adverse effects from undergoing selective bronchography.

4-Week Rule

Using the 4-week rule mentioned above, 54% of lobes that had been collapsed for > 4 weeks were reexpanded 1 week after the intervention. Of note, the lobe that had collapsed for the longest duration (24 weeks) was successfully reexpanded. Using the 4-week cutoff to predict the reversal of lobar atelectasis, the positive predictive value of the rule was 0.81, and its negative predictive value was 0.52. The sensitivity for the 4-week rule to correctly predict lobar reexpansion 1 week after intervention was 0.61 (95% CI, 0.41 to 0.78), and its specificity is 0.75 (95% CI, 0.48 to 0.93). In direct comparison, selective bronchography and the 4-week rule were significantly different in predicting which lobes would reexpand and which would not (p = 0.0026).

DISCUSSION

Selective bronchography is easy to perform and is well-tolerated by patients. An experienced operator can complete an entire selective bronchography series in 15 min without jeopardizing patient safety. No patients within the treatment group encountered significant complications related to the procedure of selective bronchography. Bronchospasm, which is a known complication of bronchography, did not occur in any patient in our population. This may have been secondary to the use of small aliquots of contrast media (ie, < 6 mL) that were diluted 50:50 with normal saline solution. The use of nonionic contrast medium could reduce the risk of bronchospasm further. Koval et al, (11) who also used ionic contrast medium, observed no complications.

The two radiographic patterns that were observed were defined as an intact bronchial tree with variable degrees of bronchiectasis or as an ill-defined collection of contrast without obvious bronchial components, which was called a blush appearance. The intact tree pattern appears to define bronchial anatomy and suggests greater potential for the restoration of that airway's function. The cause of the blush contrast pattern is not clear at this time. The appearance suggests that contrast has spread into a nonbronchial space. This space could be necrotic tumor or lung parenchyma and suggests the presence of disrupted airways.

Real-time imaging of this method revealed a spectrum of appearance that was unappreciated when examining still photographs of the technique. We strongly recommend this approach as it provides information that is invaluable for the reliable interpretation of selective bronchography. For this study, the bronchograms that were recorded as a blush pattern gave no indication of an intact tree during the injection process. An intact airway could demonstrate a hybrid tree/blush pattern if it had mucous impaction or contrast medium that had been forced too aggressively into a collapsed lobe. Aggressive contrast injection could flood the alveolar space before the appearance of a bronchial component and could appear as a blush pattern. Consistent operator technique would minimize possible alveolar flooding, and direct visualization of the distal airway is warranted when mucous impaction is suspected or a hybrid appearance is seen.

Patients with collapsed lungs and intact airways distal to a neoplastic obstruction should have the potential for the restoration of airway function with subsequent reexpansion of the ateleetatic lung once the obstruction is removed or bypassed. We were able to bypass every airway obstruction that was encountered by combinations of tumor ablation techniques, balloon dilation, and stent placement, however, airway patency at these sites did not assure reexpansion of the collapsed lung. A bronchial tree pattern suggests the presence of an intact functional airway, and reexpansion occurred in 80% of patients in whom this pattern was found and demonstrated a 0.80 positive predictive value. The postobstructive but intact airways were often bronehiectatic, but the presence or degree of bronchiectasis did not affect the reexpansion. The failure to reexpand a collapsed lung when the bronchogram revealed an intact tree seemed to correlate with the extent of tumor burden infiltrating the lung, however, this impression could not be substantiated, and the failure to reexpand the lung remains elusive. Outcomes from patients with collapsed lobes that exhibited an intact bronchial tree pattern are similar to those described by George et al (12) with some minor differences. They studied 17 patients who had endobronchial tumors involving the mainstem bronchi, whereas our patients had tumors predominately involving lobar bronchi. Only 6% of the lobes studied by George et al (12) failed to demonstrate an intact tree, whereas in our study 20% of the lobes failed to demonstrate and intact tree. George et al (12) noted that those lobes could reexpand regardless of the amount of bronchiectasis of the airways distal to the obstruction.

The blush contrast pattern had an estimated negative predictive value of 1.00 for the reversal of collapse, regardless of the duration of collapse. The collapsed lung was unaffected by interventional procedures to remove or bypass the neoplastic obstruction. In a review of the bronchographic literature, we found no description or reference to a bronchographic pattern that provided a negative predictive value for the reversal of a collapsed lung. In addition, we have found no published reports describing the blush pattern in selective bronchography. There was no correlation between the appearance of a blush or tree contrast pattern and the estimated duration of collapse (average duration for tree patterns, 6.2 weeks; average duration for blush pattern, 6.6 weeks; p = 0.83). Blush patterns were seen in patients with as little as a 2-week duration of collapse, and tree patterns were observed in patients with the longest duration of collapse.

Selective bronchography was analyzed for its sensitivity and specificity, and was compared to the time method (Fig 3). Comparison is somewhat difficult, given the imprecise duration of the atelectasis. The vertical line represents the 4-week time period that was used for clinical decisions to intervene or not to intervene when employing the time method. Sensitivity was defined as the probability of correctly identifying a patient with a resolved lobar collapse. The ability of selective bronchography to identify reversible cases is statistically superior to the time method, and the bronchographic blush pattern suggests specificity based on the estimated negative predictive value of 1.00.

Selective bronchography is a useful technique with which to study the bronchographic pattern of atelectatic lung lobes in patients with neoplastic airway obstructions who are being considered for interventional bronchoscopic procedures. The current standard is to avoid interventional procedures when atelectasis has been present for > 4 weeks because the restoration of proper function would be unlikely. The lobar pattern visualized with selective bronchography has a superior predictive value with which to determine which patients would benefit from interventions that are aimed at reexpanding neoplastic obstructive atelectatic lung. The traditional clinical guidelines for interventional pulmonary techniques have been limited to a duration of lobar or multilobar collapse of < 4 weeks, the direct visualization of the airway distal to the obstruction, or the CT scan appearance of that distal airway. Our findings employing selective bronchography refute these concepts and provide better indications for interventional therapies used to attempt the reexpansion of collapsed lobes.

Potential shortcomings of this approach include the possibility of inaccurate bronchographic interpretation and low power, which is reflected in the broad range of the CIs. Low power occurred primarily because the number of patients with a blush pattern was small. This fact establishes that further investigation of this question may be needed with a larger number of patients, specifically with a larger number of patients with blush patterns. Additionally, it could be argued that the proper supportive data for our conclusions should be derived from a randomized study.

We also recognize that operator interpretation of the selective bronchographic appearance is a potential source of error. For the purpose of this study, the determination of tree or blush pattern was made by the consensus of two of the investigators while they viewed real-time fluoroscopy. For future studies, it may be beneficial to have real-time imaging interpreted by an outside viewer or panel of experts. We think that just viewing snapshots made during the procedure without using real-time imaging did not allow the bronchoscopist to fully appreciate the distal airway anatomy.

CONCLUSIONS

In this prospective study, we found that selective bronchography was a useful method with which to ascertain that patients with postobstructive atelectasis due to a neoplasm would benefit from interventional therapies that are aimed at reexpanding their collapsed lobes. Selective bronchography demonstrated the following two distinct patterns: the tree pattern in 35 lobes, of which 28 resulted in reexpansion; and the blush pattern in 9 lobes, none of which showed reexpansion after similar interventional therapies. Selective bronchography has an excellent sensitivity and a radiographically obvious predictive value for the blush pattern. Selective bronchography is superior to the clinical guidelines currently used for the assessment of postobstructive atelectasis.

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Gordon H. Downie, MD, PhD, FCCP; Carter J. H. Childs, MD; Dante L. Landucci, MD; Imtiaz Khurshid, MD; Paul Vos, PhD; and Ralph Whatley, MD, FCCP

* From the Section of Pulmonary and Critical Care Medicine (Drs, Downie, Childs, Landucci, Khurshid, and Whatley), Department of Internal Medicine, The Brody School of Medicine, and the Department of Biostatistics (Dr. Vos), School of Allied Health Sciences, East Carolina University, Greenville, NC. Manuscript received March 21, 2002; revision accepted September 20, 2002.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Gordon H. Downie, MD, PhD, FCCP, Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Brody School of Medicine, East Carolina University, Greenville, NC 27858; e-mail: downieg@mail.ecu.edu

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