Flexible bronchoscopy is performed frequently in patients with underlying pulmonary dysfunction, but there have been few recent evaluations of its safety in this setting. Chronic obstructive pulmonary disease (COPD) often coexists with conditions that require diagnostic bronchoscopy and has been listed by the British Thoracic Society as needing caution.1 Although there is a general impression that bronchoscopy is well tolerated and has low morbidity, several factors suggest that a reappraisal of its safety in patients with chronic lung disease is needed. Previous investigations were generally retrospective in nature, with a paucity of objective physiological measures in either controls or COPD patients and antedated recent major advances in the diagnosis and treatment of COPD. Moreover, there has been considerable technologic progress in flexible bronchoscopy as it is performed for broader diagnostic and therapeutic indications and numerous improvements in instrumentation and patient selection have occurred. Finally, aging of the population, with an increasing prevalence of chronic lung disease, requires further data to better inform risk:benefit decisions. To assess the current risk imparted by COPD, we gathered data on patients undergoing moderate sedation bronchoscopy with attention to complications during and after the procedure.
PATIENTS AND METHODS
Following Institutional Review Board approval and with informed consent, at our tertiary care university medical center, we prospectively followed patients during and 7 days after moderate sedation flexible bronchoscopy with a focus on complications. Bronchoscopy was performed by experienced bronchoscopists or trainees under direct supervision for various indications on adult patients. Moderate sedation was achieved with fentanyl and midazolam when indicated. No specific preprocedural medication is routinely administered based on a history of COPD. Outpatient medical regimens were maintained in patients with COPD. Diagnostic modalities including lavage, brush, and biopsies were performed at the discretion of the attending physician based upon patients’ clinical presentation as well as goals and tolerance of the procedure.
Patients were documented as having COPD if the diagnosis was present on their medical record and consistent with pulmonary function testing (PFT) results. An obstructive pattern was defined as FEV1/FVC<70% (forced expiratory volume in the first second/forced vital capacity). Severity was defined using Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines: mild (FEV1≥80% predicted), moderate (50%≤FEV1<80%), severe (30%≤FEV1<50%), and very severe (FEV1<30%).2,3
Complications were recorded prospectively and included those during and immediately following bronchoscopy. Patients were contacted by telephone to determine whether any complications had occurred within 1 week after the procedure.
Statistical analyses were performed using JMP (SAS Institute Inc., Cary, NC). We compared COPD to nonobstructive patients and compared different severities of COPD. Results are presented as percentages and means±SDs. Continuous variables were compared among groups using ANOVA models and, where a signal was present, groups were compared with the Wilcoxon tests. Nominal variables were analyzed using the χ2 tests for association. Multivariate analysis was performed to adjust for age, body mass index, and use of home oxygen. Results were considered significant when the P-value was ≤0.05.
From January 2010 through December 2010, a total of 668 patients underwent bronchoscopy of whom 258 were prospectively enrolled. In the entire study group, 151 (63%) had prior PFTs and these were ultimately part of the analysis (Fig. 1). The majority (53%) were outpatients. A clinical diagnosis of COPD was present in 67 patients (44%). By spirometric severity, there were 6 mild (9%), 29 moderate (42%), 27 severe (41%), and 5 very severe (8%) COPD patients. Demographics and patient characteristics are displayed in Table 1. The COPD group had a lower mean FEV1% predicted and higher use of home oxygen. As per GOLD guidelines,2,3 patients with COPD received an inhaled medical regimen appropriate for the severity of their disease (Fig. 2). Patients with COPD were more likely to be on long-acting β-agonists (57% vs. 12%), inhaled corticosteroids (57% vs. 11%), and inhaled anticholinergics (63% vs. 7%) (all P<0.001).
Table 2 gives details about the bronchoscopy. Average bronchoscopy procedure time and recovery time was not different in patients with or without COPD. Less sedation was administered in COPD patients compared with patients without COPD. Indications for bronchoscopy differed in patients undergoing bronchoscopy with and without COPD (Fig. 3). Patients with COPD more often underwent bronchoscopy for lung masses or nodules (37%) or cough with or without hemoptysis (25%), whereas patients without COPD underwent bronchoscopy for evaluation of unexplained pulmonary infiltrates (51%). Accordingly, patients with COPD were more likely to have brushings and endobronchial biopsies (30% and 12%, respectively), whereas patients without COPD were more like to have bronchoalveolar lavage and transbronchial lung biopsy (69% and 8%, respectively). Early termination of the procedure occurred in 4% (n=3) of patients with COPD and 6% (n=5) of patients without COPD (P=0.69). The 3 patients with COPD and earlier termination all had very severe classification.
Overall, complications were rare with a 5% major complication rate: 7 respiratory failure (defined as increasing oxygen requirement with escalation of care; 3 of the 7 required intubation and mechanical ventilation), 1 patient with hemoptysis requiring hospital admission who also developed a pneumothorax within 24 h of the procedure. There were no deaths. The minor complication rate was 13% (including bronchospasms, desaturation episodes, early termination of procedure, minor hemoptysis, hypotension, and medication reaction). Table 3 demonstrates the difference in complications between patients with COPD and patients without COPD. There were significantly more respiratory complications (bronchospasm, desaturations resulting in hospitalization or transfer to higher level of care, pneumothorax, and respiratory failure) in patients with severe to very severe COPD (22%) compared with patients without COPD (6%) (P=0.018). The pneumothorax occurred following brushings and endobronchial biopsies. Among patients with COPD, the frequency of respiratory complications tended to be higher in those with severe to very severe COPD (22%) than patients with mild to moderate COPD (3%), but that did not reach clinical significance. In multivariate analysis adjusting for age, body mass index, and use of home oxygen, the difference in respiratory complications in patients with severe to very severe COPD was still statistically significantly higher than in patients without COPD (P=0.045) (Fig. 4).
Our complication rate for all patients undergoing flexible bronchoscopy was found to be 13% for minor complications and 5% for major complications, and no deaths occurred. Bronchoscopy is known to have a good safety profile with complication rates of 0.1% to 5%,4–6 which have been shown to vary based on type of procedure,4,7 skill of the performing bronchoscopist,5 and existing comorbidities.7 Complication rates in large retrospective reviews range from 0.3% to 0.8% for patients undergoing bronchoscopy.8,9
Surprisingly, few studies have reported the complication rate of bronchoscopy as it relates to patients with objectively defined COPD. Moreover, PFT results in control patients without COPD were not reported in prior studies. Hattotuwa et al10 reported on 57 patients with COPD undergoing research bronchoscopy. There were 5 adverse events including bronchospasm, pneumothorax, hemoptysis, and pleuritic chest pain. In total, there was a 2% major complication rate requiring hospital treatment and a 3% minor complication rate requiring no intervention. There was no control group for comparison. Neuman et al11 demonstrated a higher risk of hemoglobin oxygen desaturation in patients with COPD who also had pulmonary hypertension (24% vs. 7%, P=0.033), but there was no non-COPD comparison group. In the sham bronchoscopy arm of a bronchoscopic lung volume reduction study using moderate sedation in patients with emphysema, the respiratory complication rate was 16% (3 with exacerbations requiring hospitalization, 1 pneumothorax). Mean FEV1% predicted in this group was 30%.12 Chechani13 found that 11 of 20 hypercapnic patients with COPD had bronchospasm requiring albuterol postbronchoscopy, and 4 required early termination of the procedure due to bronchospasm. Stoltz et al14 performed bronchoscopy on 80 COPD patients (15% mild, 43% moderate, 32% severe, and 10% very severe) to trial pretreatment with a long-acting β-agonist. They had no major complications and noted a 9% rate of hemoglobin oxygen desaturations with bronchoscopy.
More respiratory complications occurred in our patients with objectively defined severe and very severe COPD. A recent review found a paucity of reports in patients with severe to very severe obstructive lung disease (FEV1<35%).15 One study of 19 patients with COPD (mean FEV1 of 31%) predicted had a 21% complication rate while undergoing flexible bronchoscopy for endobronchial valve placement.16 Another investigation solely on COPD patients (mean FEV1 37% predicted) reported “no serious complications” during bronchoscopy, but noted that 14 patients had been excluded from bronchoscopy due to excessive risk.17 Most recently, Crawford et al18 reported on bronchoscopy safety in a lung cancer risk test trial, where 155 patients had PFT-proven COPD (37 with severe to very severe). Although they report no severe adverse events, mild adverse events were not delineated by the presence or absence of obstructive disease.
Our observations demonstrate a similar rate of complications among patients with COPD to these other prospective studies and extend knowledge regarding the safety of the procedure in this setting. Despite a rigorous prospective recording of complications that included minor events without clinical impact and an extended period of follow-up of a week after bronchoscopy, the likelihood of complications was low in our patients and similar to persons without COPD. Patients with severe to very severe COPD had more respiratory complications compared with those without COPD. The significance was retained even when adjusted for age, body mass index, and use of home oxygen. These observations are consistent with evidence statements and recommendations of the British Thoracic Society regarding bronchoscopy in patients with COPD.
In their guideline for diagnostic flexible bronchoscopy in adults, the British Thoracic Society has recommended that COPD treatment be optimized before bronchoscopy when possible, and that bronchoscopists should be cautious when sedating patients with COPD (both Grade D recommendations).1 Both of these recommendations were observed in our experience as COPD patients had been treated with appropriate inhaler therapy, and the COPD patients had received less sedation than the non-COPD patients. We did not routinely give preprocedural oral steroids and randomized studies with steroids use may be useful to determine whether oral steroids in this population reduce respiratory complications.
The use of more airway-focused sampling procedures and indications for bronchoscopy in our patients are consistent with one another and relationships of lung cancer to COPD. It is noteworthy that complications in COPD patients were low despite such increased airway sampling. Although the indication for bronchoscopy differed in patients with and without COPD and instrumentation during bronchoscopy was slightly different, procedure time was not different. Patients with COPD received less sedation and analgesics. It is not clear whether bronchoscopists had purposefully minimized sedation administration because of the presence of COPD. In addition, our study is limited to patients selected for flexible bronchoscopy and does not assess patients in whom clinical status and COPD severity was believed to preclude bronchoscopy. Because patients evaluated were undergoing moderate sedation bronchoscopy of abbreviated duration, the outcomes of longer procedures with advanced diagnostic techniques and/or general anesthesia are unknown. Also, we excluded patients in whom PFT was not available, so we cannot comment about this population’s complications. In addition, we do not have data on patients deemed too high risk for bronchoscopy by our pulmonologists. The overall complication rate was higher than some retrospective reviews, but the prospective nature of our data has been shown to demonstrate higher—perhaps more accurate—complication rates.8 Moreover, our rigorous inclusion of relatively minor events as complications contributes to this higher frequency.
In summary, our results confirm historical impressions of the overall good safety profile of bronchoscopy in patients with COPD. In patients with severe to very severe COPD who underwent flexible bronchoscopy the respiratory complication rate was higher compared with patients without COPD. This observation supports current guidelines that risk should be taken into consideration when performing moderate sedation flexible bronchoscopy in these patients.
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