Atul C. Mehta

Transbronchial needle aspiration : An underused diagnostic technique

Despite its proven usefulness, TBNA is not widely used. An American College of Chest Physicians (ACCP) survey showed that only 11.8% of pulmonologists use TBNA. Most pulmonologists in the 1980s were not formally trained in TBNA. This lack of training has unfortunately translated to minimal emphasis on TBNA in current training programs in a large number of institutions. Technical problems with the procedure (faulty site selection, incomplete needle penetration, catheter kinking that prevents adequate suction, etc.), the confusing array of needles, low diagnostic yields, unproven concerns regarding the safety of the procedure, inadequate cytopathology support, and bronchoscopic damage have all perpetuated the image of limited usefulness for this procedure. Limitations to the practice of TBNA are: Lack of training during fellowship Technical inadequacies Lack of cytopathologists trained in TBNA interpretation Fear of bronchoscope damage Safety issues Failure to reproduce published successes Reservations regarding usefulness of TBNA results Hands-on experience with TBNA, developing familiarity and expertise with only a few needles, and paying careful attention to anatomy, procedure techniques, and specimen acquisition may all help to increase yield. The following lists how better results can be obtained with TBNA: Preprocedure Review TBNA instruction tapes Attend hands-on courses Practice with lung models Review patients CAT scans Familiarize with one-two cytology and histology needle Obtain a trained assistant Procedural Identify target site Needle to airway angle at least greater than 45 degrees Insert entire length of the needle Use scope channel to support the catheter Release suction before withdrawing needle (for staging) Specimen acquisition Avoid delay in preparing slides Adequate sampling (at least two) Use smear method for cytology specimen Analyze all samples flush solutions cell block Postprocedure Find an experienced cytopathologist Review your procedure (by watching video) Review pathology slides Acquisition of skills with cytology needles should precede the use of the histology needle. Increasing education and experience can also increase diagnostic yields. Transbronchial needle aspiration has been proven to be accurate in staging lung cancers, identifying inoperable carcinomas, and diagnosing a variety of lung diseases. Few complications have been encountered and the technique is less invasive and less costly than surgical procedures. Drawing on evidence from published literature, we suggest the following guidelines for TBNA: All patients presenting with mediastinal or hilar adenopathy or both, should have 22-ga and/or 19-ga TBNA as the initial procedure. These procedures would help diagnose malignant and nonmalignant diseases, and stage lung cancers. All patients with evidence of submucosal and peribronchial disease should have 22-ga needle cytology sampling. In patients with visible endobronchial disease, 22-ga TBNA should be optional. In the presence of a necrotic or a hemorrhagic tumor, or in a patient with a bleeding diathesis, TBNA would be helpful. In all patients with Type III and IV peripheral nodules, TBNA should be the initial diagnostic procedure. There remains no doubt about the diagnostic usefulness of TBNA. Guidelines must be developed to ensure that pulmonary fellows are adequately trained in this procedure. Regional workshops with hands-on experience targeted to practicing pulmonologists organized by the ACCP would help popularize the procedure. Initial low yields should not discourage pulmonologists from using the procedure. Collaboration between thoracic surgeons, oncologists, and pulmonary physicians is essential to set up TBNA programs within institutions. With time, as more and more pulmonologists attain expertise in TBNA, the full potential of this nonsurgical, cost-effective, and safe procedure will be realized.

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.

Cytomegalovirus Infection Is a Risk Factor for Invasive Aspergillosis in Lung Transplant Recipients

Invasive aspergillosis (IA) remains a major cause of morbidity and mortality following solid organ transplantation. To assess the incidence of IA following lung transplantation and to identify risk factors for its occurrence, we performed a case-control study involving 101 patients undergoing lung transplantation at our institution from 1990 to 1995 and reviewed the findings. Fourteen patients (14%) developed IA. The mean time from transplantation to diagnosis was 15 months. Nine patients died; the mean time to death from diagnosis was 13 days. Risk factors associated with developing IA included concomitant cytomegalovirus (CMV) pneumonia or viremia and culture isolation of Aspergillus species from a respiratory tract specimen after lung transplantation. Optimal strategies to prevent IA in lung transplant recipients remain to be determined, but prevention of aspergillus airway colonization and CMV viremia and disease after transplantation may be important targets for prophylactic interventions.

Gorham's syndrome: A case report and review of the literature

Gorhams syndrome is a rare disorder involving a proliferation of vascular channels associated with extensive loss of bony matrix. A case report is presented with a review of the 97 previously reported cases. The age of patients at presentation has ranged from less than one to 75 years (mean: 27 years). Sixty-four percent have been men. Fifty-seven percent have had a history of prior trauma. Laboratory values for systemic measures have usually been normal. The disease usually arrests spontaneously, but this is unpredictable. Sixteen patients (16 percent) have died of the disorder, with 10 deaths due to chest wall involvement, three to spinal cord transection, two to sepsis, and one to asphyxia and aspiration. Although the mechanism of bone loss is unknown, osteoclasts were focally increased in the case described herein. Further information and investigation are needed to better understand this unusual disorder.

Electromagnetic Navigation during Flexible Bronchoscopy

Background: Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. Objectives: To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. Methods: Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 × 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. Results: The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. Conclusions: Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.

Adult airway foreign body removal. What's new?

Signs and symptoms of adult FB aspiration are most often nonspecific. Misdiagnosis and delay in diagnosis frequently occur. Radiographic evaluation is helpful, but flexible bronchoscopy is the gold standard in the identification and localization of an airway foreign body. With increasing experience and development of better accessories, removal using a flexible bronchoscope under local anesthesia can be performed safely and successfully. Review of large series of FB removal indicates a success rate of 86% in more than 400 procedures with flexible bronchoscopy.

Hypogammaglobulinemia in lung transplant recipients

Background. Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients.Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels. Methods. All lung transplant recipients followed at a single center between October 1996 and June 1999 underwent a posttransplant humoral immune status survey as part of routine posttransplant follow-up. This survey consists of total immunoglobulin levels (IgG, IgM, IgA), IgG subclasses (IgG1–4), and antibody titers to Pneumococcus, diphtheria, and tetanus. Since February 1997, this survey has been incorporated into the pretransplant evaluation as well. Humoral survey results for October 1996 through July 1999 were recorded, and clinical information on major infectious disease outcomes was obtained from chart reviews, discharge summaries, the Cleveland Clinic Unified Transplant Database, and review of all microbiological studies and pathology results for each patient. Results. Of 67 patients with humoral immune surveys drawn posttransplant, 47 (70%) had IgG levels less than 600 mg/dl (normal 717-1410 mg/dl), of which 25 (37%) had IgG levels less than 400 mg/dl (“lowest IgG group”) and 22 (33%) had IgG levels between 400 and 600 mg/dl (“moderately low IgG group”). A total of 20 patients (30%) had IgG levels of more than 600 mg/dl (“normal IgG group”). Infections that were significantly more common in the lowest IgG group, and more common in the moderately low IgG group than the normal IgG group, included: number of pneumonias (P =0.0006), bacteremias (P =0.02), total bacterial infections (P =0.002), tissue-invasive cytomegalovirus (P =0.01), invasive aspergillosis (P =0.001), total fungal infections (P =0.001), and total infections (P =0.006). Median hospital days per posttransplant year was significantly different in the three groups (11.0 vs. 7.4 vs. 2.8 days, P =0.0003.) Invasive aspergillosis occurred in 44% of the lowest IgG group, 9% of the moderately low IgG group, and 0% of the normal IgG group (P <0.001). Survival was poorest in the lowest IgG group and intermediate in the moderately low IgG group. IgG subclass deficiencies occurred in a variety of patterns. Hypogammaglobulinemic patients lacked protective responses to Pneumococcus in 14/47 (30%), diphtheria in 15%, and tetanus in 19%. In a group of 48 patients screened pretransplant, 90% had normal immunoglobulin levels. Conclusions. Hypogammaglobulinemia in lung transplant recipients is more common than has been previously recognized. An IgG level of less than 400 mg/dl identifies a group at extremely high risk of bacterial and fungal infections, tissue-invasive cytomegalovirus, and poorer survival. Immunoglobulin monitoring may offer an opportunity for intensive surveillance, tapering of immunosuppression, and preemptive therapy for infection.

STENTING OF THE TRACHEOBRONCHIAL TREE

Endoscopic treatment of endobronchial obstructions is becoming increasingly important. Tracheobronchial stents often are needed in the treatment of obstructions from submucosal or extrabronchial lesions. Tube stents have been available since the early 1960s but are underused because their insertion requires the use of a rigid bronchoscope. With the recent development of metallic stents, interventional radiologists increasingly are involved in the treatment of tracheobronchial obstructions. Metallic stents, easily placed with flexible bronchoscopy, are growing in popularity. All available tracheobronchial stents have been shown in various clinical series to be able to achieve immediate resolution of respiratory symptoms from various tracheobronchial obstructions. A stents performance, however, should not be based solely on short-term response. Presently, there is no ideal stent because none is free of complications and none are able to consistently maintain life-long patency. Gianturco stents are associated with serious major complications (bronchial perforations and strut fractures) and are no longer recommended for use in the tracheobronchial tree. The Palmaz stent has also fallen into disfavor, because a strong external force, such as a vigorous cough, can recompress it. The Strecker stent can only be used in smaller airways, but may be useful in the accurate stenting of short segment stenoses because it does not foreshorten on deployment. The Wallstent and Ultraflex are our present metallic stents of choice. Both are easy to deploy, available in covered forms, exert adequate radial force, remain relatively stable in position, and have good longitudinal flexibility for use in tortuous airways. Disadvantages include excessive granulation tissue formation and difficulty of removal once the stent has been epithelialized. Metallic stents should be chosen very carefully for use in benign lesions with ongoing active local inflammation or when temporary stenting is needed. In the absence of an ideal stent, technologic advancements will continue. Potential developments include removable metallic stents, biodegradable stents, and chemically and radioactively coated stents. Unquestionably, the expanding stent market will drive scientific research toward the development of the ideal stent. Clearly, physicians need to be ready to assess these technologic advancements.

A Multicenter Pilot Study of a Bronchial Valve for the Treatment of Severe Emphysema

Background: Chronic obstructive pulmonary disease (COPD) affects millions of people and has limited treatment options. Surgical treatments for severe COPD with emphysema are effective for highly selected patients. A minimally invasive method for treating emphysema could decrease morbidity and increase acceptance by patients. Objective: To study the safety and effectiveness of the IBV® Valve for the treatment of severe emphysema. Methods: A multicenter study treated 91 patients with severe obstruction, hyperinflation and upper lobe (UL)-predominant emphysema with 609 bronchial valves placed bilaterally into ULs. Results: Valves were placed in desired airways with 99.7% technical success and no migration or erosion. There were no procedure-related deaths and 30-day morbidity and mortality were 5.5 and 1.1%, respectively. Pneumothorax was the most frequent serious device-related complication and primarily occurred when all segments of a lobe, especially the left UL, were occluded. Highly significant health-related quality of life (HRQL) improvement (–8.2 ± 16.2, mean ± SD change at 6 months) was observed. HRQL improvement was associated with a decreased volume (mean –294 ± 427 ml, p = 0.007) in the treated lobes without visible atelectasis. FEV1, exercise tests, and total lung volume were not changed but there was a proportional shift, a redirection of inspired volume to the untreated lobes. Combined with perfusion scan changes, this suggests that there is improved ventilation and perfusion matching in non-UL lung parenchyma. Conclusion: Bronchial valve treatment of emphysema has multiple mechanisms of action and acceptable safety, and significantly improves quality of life for the majority of patients.

Should lung transplantation be performed using donation after cardiac death? The United States experience

OBJECTIVE We compared 1) survival after lung transplantation of recipients of donation after cardiac death (DCD) versus brain death donor organs in the United States and 2) recipient characteristics. METHODS Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to May 2007. Follow-up after DCD lung transplantation extended to 8.6 years, median 1 year. Differences among recipients of DCD versus brain death donor organs were expressed as a propensity score for use in comparing risk-adjusted survival. RESULTS A total of 14,939 transplants were performed, 36 with DCD organs (9 single, 27 double). Among the 36 patients, 3 have died after 1 day, 11 days, and 1.5 years. Unadjusted survival at 1, 6, 12, and 24 months was 94%, 94%, 94%, and 87%, respectively, for DCD donors versus 92%, 84%, 78%, and 69%, respectively, for brain death donors (P = .04). DCD recipients were more likely to undergo double lung transplantation and have diabetes, lower forced 1-second expiratory volume, and longer cold ischemic times. Once these were accounted for and propensity adjusted, survival was still better for DCD recipients, although the P value equals .06. CONCLUSION Concern about organ quality and ischemia-reperfusion injury has limited the application of lung DCD. However, DCD as practiced in the United States results in survival at least equivalent to that after brain death donation. It also demonstrates selection bias, particularly in performing double lung transplantation, making generalization regarding survival difficult. Nevertheless, the data support the expanded use of DCD.