Training bronchoscopists for the new era.

Gustav Killian introduced bronchoscopy a little more than a century ago. At that time, the only way others could learn to perform bronchoscopy was by one-on-one tutoring, using a rigid bronchoscope with no side portals and no imaging devices such as a television camera and monitor. One-on-one teaching remains an integral part of learning how to perform bronchoscopy well, but many new technologies have emerged that make it far less labor intensive to train bronchoscopists. This article focuses on the training of bronchoscopists for the new era.

Bronchoscopy training: current fellows' experiences and some concerns for the future.

OBJECTIVES: To determine current pulmonary fellows' perspectives about their bronchoscopy training. DESIGN: Survey of 59 pulmonary fellows selected by training program directors to represent their institutions. SETTING: "Hands-on" symposium at the CHEST 1998 annual meeting, Toronto, Canada. RESULTS: Fellows reported a mean (+/- SD) of 2.4+/- 0.7 years of training, estimated they had performed 77.7+/-34 bronchoscopies per year, and had generally high estimates of their bronchoscopy proficiency and training. Proficiency estimates correlated with number of procedures cited (r = 0.43, p = 0.001) or level of fellowship training (r = 0.40, p = 0.002). Proficiency ratings (r = 0.63, p = 0.0001) and procedure numbers (r = 0.45, p-0. 0004) correlated with program quality ratings. Approaches to bronchoscopy instruction varied, and most often consisted of one-to-one instruction by faculty (92.5%), lecture-based instruction (74.6%), and case discussions (72.9%). Use of bronchoscopy lectures (p = 0.008) or videos (p = 0.057) were associated with higher self-estimates of proficiency, whereas use of lectures (p = 0.002), a bronchoscopy text (p = 0.009), and one-on-one instruction (p = 0.05) were associated with more highly ranked programs. Major components of training varied among programs. Although most fellows had received instruction encompassed in basic bronchoscopy, fewer had experience with bronchoscopic intubation (71.2%), transbronchial needle aspiration (72.9%), quantitative bacterial culture (64.4%), stent placement (27.1%), laser photocoagulation (25.4%), or cryotherapy (6.8%). Components of bronchoscopy experiences correlated with fellows' estimates of bronchoscopy proficiency and program quality. CONCLUSIONS: Approaches to bronchoscopy instruction and the components of bronchoscopy experiences vary considerably among institutions and are associated with pulmonary fellows' perceptions of bronchoscopy proficiency and training program quality. Definition of an optimum bronchoscopy curriculum remains necessary.

Risk factors and outcomes associated with identification of Aspergillus in respiratory specimens from persons with HIV disease. Pulmonary Complications of HIV Infection Study Group.

STUDY OBJECTIVES: To examine the significance of previously suggested risk factors and assess outcomes associated with Aspergillus identification in respiratory specimens from HIV-seropositive individuals. DESIGN: This was a nested case-control study. Patients who had Aspergillus species identified in respiratory specimens were matched at the time of study entry 1:2 with control subjects according to study center, age, gender, race, HIV transmission category, and CD4 count. SETTING: The multicenter Pulmonary Complications of HIV Infection Study. PARTICIPANTS: HIV-seropositive study participants. MEASUREMENTS AND RESULTS: Between November 1988 and March 1994, Aspergillus species were detected in respiratory specimens from 19 (1.6%) participants. The rate of Aspergillus identification among participants with CD4 counts <200 cells per cubic millimeter during years 2 through 5 after study entry ranged from 1.2 to 1.9%. Neutropenia, a CD4 count <30 cells per cubic millimeter, corticosteroid use, and Pneumocystis carinii infection were associated with subsequent identification of Aspergillus in respiratory specimens. Cigarette and marijuana use, previously suggested risk factors, were not associated with Aspergillus respiratory infection. A substantially greater proportion of patients with Aspergillus compared with control subjects died during the study (90% vs 21%). Excluding four cases first diagnosed at autopsy, 67% died within 60 days after Aspergillus was detected. CONCLUSIONS: Although Aspergillus is infrequently isolated from HIV-infected persons, the associated high mortality would support serious consideration of its clinical significance in those with advanced disease and risk factors.

Cancer incidence among an HIV-infected cohort. Pulmonary Complications of HIV Infection Study Group.

Malignancies, particularly Kaposi's sarcoma and non-Hodgkin's lymphoma (NHL), are associated with human immunodeficiency virus (HIV) infection. Cancer incidence among 1,073 asymptomatic HIV-infected individuals from the Pulmonary Complications of HIV Infection Study cohort, persons from six states followed from 1988 to 1994, was examined. Total cancer incidence was 3.99/100 person-years; for Kaposi's sarcoma, incidence was 2.64 cases/100 person-years, and for NHL, it was 1.18 cases/100 person-years. Total cancer (n = 156 cases) was higher among nonblacks than among blacks (rate ratio = 2.8, 95% confidence interval 1.3-6.1), with similar results for Kaposi's sarcoma and NHL. The rate of lung cancer (n = 5) among white, homosexual/bisexual males was 0.18 per 100 person-years, suggesting a high risk of lung cancer.

Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

Intensive care of patients with HIV infection: utilization, critical illnesses, and outcomes. Pulmonary Complications of HIV Infection Study Group.

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

A study of HIV RNA viral load in AIDS patients with bacterial pneumonia.

We examined the effect of bacterial pneumonia on the magnitude of circulating plasma HIV RNA in HIV-infected patients. Serum samples from 13 adult HIV-infected patients (median CD4 count = 83 cells/microl) were assayed for HIV RNA using the reverse transcriptase polymerase chain reaction assay (a) before bacterial pneumonia, (b) during the acute phase, and (c) after the recovery from the disease. Patients remained on constant antiretroviral therapy: HIV RNA was detected in all samples tested. The medians before, during, and after bacterial pneumonia were 60,000 copies per ml, 245,000 copies per ml, and 84,000 copies per ml, respectively. All 13 patients had increased HIV RNA levels on developing pneumonia. There was a decline in the level of HIV RNA with recovery from pneumonia in 12 of 13 patients. The difference between the HIV RNA levels before and after pneumonia was not significant, nor was there significant difference in the CD4 counts before and after pneumonia. In conclusion, bacterial pneumonia is associated with a consistent, transient increase in HIV RNA of variable magnitude in AIDS patients. Interpretation of HIV RNA changes for clinical management of AIDS patients must take into account this reversible elevation during infections.

Bronchoscopic biopsies and bronchoalveolar lavage.

Bronchoscopy with biopsies, bronchoalveolar lavage, and other sampling techniques are frequently needed to establish definitive diagnoses of pulmonary disorders. Combinations of specimens provide superior results to single specimens alone for lung cancer, including those which are endoscopically visible and peripheral in location. Transbronchial biopsy is useful to establish tissue diagnoses in certain diffuse parenchymal lung diseases with specific recognizable histologic patterns such as sarcoidosis or eosinophilic granuloma, but it is less useful for disorders such as interstitial pulmonary fibrosis. Patients with tuberculosis can be diagnosed by performing bronchoscopy, but other sampling techniques are equally good and safer for the bronchoscopist and other health care workers. Bronchoalveolar lavage is especially valuable for confirming infectious complications in immunocompromised hosts, and it also has great potential to elucidate basic mechanisms of pulmonary diseases in research applications.

Long-term survival following surgical treatment of solitary brain metastasis in non-small cell lung cancer.

Dissemination of lung cancer beyond the intrathoracic lymph nodes (stage IV disease) implies surgical unresectability. However, solitary brain metastases (SBMs) from non-small cell lung cancer (NSCLC) have often been treated by combined resection of the primary tumor and its metastasis. Such an aggressive approach appears to substantively improve patient outcome and provide better quality of life in selected cases. A search of the literature reveals extended survival (10 years or longer) in 16 patients following combined surgical excision. We report three patients with NSCLC and isolated central nervous system involvement who achieved exceptionally long survival. The existing literature on SBMs from NSCLC is reviewed.

Castleman's disease.

OBJECTIVE: To describe the two variants of Castleman's disease--the hyaline-vascular type and the plasma-cell type--and discuss the associated histologic features. DESIGN: We present a case of the hyaline-vascular type and review the literature. RESULTS: Castleman's disease was once thought to be localized and self-limited, but in recent years, reports have described a multicentric variety with severe systemic manifestations and, at times, an inexorable clinical course. Unlike the localized type for which surgical excision is curative regardless of the histologic type, multicentric disease often necessitates aggressive systemic therapy and portends a poor outcome. Little is known about the cause of this disorder, but the bulk of evidence points toward faulty immunoregulation that results in excessive proliferation of B lymphocytes and plasma cells in lymphoid organs. CONCLUSION: Castleman's disease is rare and poorly understood. The diagnosis is "contextual" and must be considered in the appropriate clinical setting and only after all other causes of lymphadenopathy have been investigated and excluded. The optimal therapeutic regimen is unknown.

Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. METHODS: In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men. RESULTS: There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P < 0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P < or = 0.022 for each comparison). Injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners. In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others. Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P = 0.007). CONCLUSIONS: Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users.

Pulmonary function tests in HIV-infected patients without AIDS. Pulmonary Complications of HIV Infection Study Group.

To determine the prevalence, incidence, and types of lung diseases that occur in association with HIV infection, 1,353 subjects, including HIV-seropositive homosexual men, injection drug users, female sexual partners of HIV-positive men, and HIV-seronegative control subjects from the first two transmission categories were evaluated prospectively in a multicenter study. Patients with AIDS at the time of initial evaluation were excluded. One thousand two-hundred ninety-four subjects who had no AIDS-defining diagnosis within 3 mo of enrollment had measurements of FVC, FEV1 and DLCO at the time of enrollment. As a group, all subjects had mean values of FVC and FEV1 close to 100% predicted. Those with CD4 counts below 200/mm3 had slightly reduced DLCO compared with the others. Subjects with a history of HIV-associated symptoms (thrush, weight loss, herpes zoster) also had a reduced DLCO compared with those without symptoms. Injection drug users had reduced FVC, FEV1 and DLCO compared with homosexual men and female sexual partners of HIV-infected men, with DLCO more substantially reduced. Part of the reduction in DLCO in drug users was attributable to factors other than HIV infection, especially cigarette smoking and race. Using predicted values that take cigarette smoking into account, the prevalence of abnormality in DLCO was higher among injection drug users (33.3%) than among homosexual men (11.2%) and female sexual partners (12.7%). These results show that advanced HIV infection, characterized by CD4 count < 200/mm3 or HIV-associated symptoms, and factors unrelated to HIV infection, including race, cigarette smoking, and injection drug use, are all associated with reductions in DLCO measurements.

Routine analysis of induced sputum is not an effective strategy for screening persons infected with human immunodeficiency virus for Mycobacterium tuberculosis or Pneumocystis carinii. Pulmonary Complications of HIV Infection Study Group.

A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M. tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity.

Respiratory illness in persons with human immunodeficiency virus infection. The Pulmonary Complications of HIV Infection Study Group.

Although the pulmonary complications of advanced human immunodeficiency virus (HIV) infection have been well described, there is little information on respiratory manifestations of earlier disease. This report describes the respiratory disorders diagnosed over an 18-month period in a cohort of persons with or at risk for HIV infection with variable immunologic status. Cohort members were followed routinely and evaluated for respiratory disease by standard diagnostic algorithms. The 18-month incidence of each respiratory diagnosis was determined, and for frequent diagnoses, incidence by transmission category, location of residence, smoking status, CD4 count, and performance score at entry were compared. The most frequent respiratory diagnoses in HIV-seropositive cohort members were common to the general population: upper respiratory infection (33.4%), acute bronchitis (16.0%), acute sinusitis (5.3%), and bacterial pneumonia (4.8%). Pneumocystis carinii pneumonia occurred in 3.9%. Ambulatory respiratory illnesses were reported frequently regardless of immunologic status. The rates of P. carinii pneumonia and bacterial pneumonia were significantly greater in cohort members with entry CD4 counts < 250. Bacterial pneumonia occurred more frequently in injecting drug users and in cohort members with entry Karnofsky scores < 90. Disease stage and demographic and exposure factors are important variables affecting the respiratory manifestations of HIV infection.

A decline in the pulmonary diffusing capacity does not indicate opportunistic lung disease in asymptomatic persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group.

We enrolled 1,353 subjects in a multicenter study to evaluate the spectrum of pulmonary complications associated with human immunodeficiency virus (HIV) infection and the feasibility of detecting pulmonary infections in asymptomatic members of this group. There were 1,171 who were HIV-seropositive; the remaining 182 were HIV-seronegative, but they belonged to high-risk transmission groups (homosexual/bisexual, or injection drug users). Single-breath carbon monoxide diffusing capacity (DLCO) was measured serially (at 3- to 12-month intervals) in a prospective fashion to determine whether a decline of > or = 20% predicted the presence of Pneumocystis carinii pneumonia or other pulmonary infections in the absence of new pulmonary symptoms and no new abnormalities on chest roentgenograms. In 64 subjects (6% of the group who had two or more measurements) DLCO declined > or = 20% from a prior value within 2 yr of entry, unassociated with fever, increased cough or dyspnea, or new chest roentgenogram abnormalities. Induced sputum was analyzed for the presence of P. carinii and mycobacteria in 44; fiberoptic bronchoscopy was performed with bronchoalveolar lavage in 14, six of whom also had transbronchial lung biopsy. All 64 subjects with the asymptomatic decline in DLCO were followed for an additional 3 to 12 months with additional clinical evaluations, chest roentgenograms, and DLCO determinations, or until death (one subject). In no case was the decline in DLCO due to P. carinii pneumonia or other pulmonary infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of brachytherapy in the management of pulmonary and mediastinal malignancies.

Brachytherapy, the permanent or temporary implantation of radioactive sources, has been performed in limited numbers of patients with lung cancer over the last 50 years. Because of renewed interest in this modality, we reviewed our experience with 103 patients treated over a 7-year period. The mean age of this group was 55.5 years (range, 1 to 84 years). Primary lung cancer accounted for 82 patients (79.6%); metastatic lesions to the lung, 13 (12.6%); and mediastinal malignancies, 8 (7.8%). Indications for brachytherapy included mediastinal and chest wall invasion in 42 patients (40.8%), unresectable tumors and mediastinal adenopathy in 30 (29.1%), medical contraindications to extensive pulmonary resection in 20 (19.4%), and irradiation of excised lymph node beds in 11 (10.7%). Seeds labeled with radioactive iodine 125 alone were used in 65 patients (63.1%), afterloading catheters containing iridium 192 sources in 25 (24.3%), and both in 13 (12.6%). There were no operative deaths. With a mean follow-up of 18.6 months, the mean and median survivals for the entire group were 17.3 and 14.0 months, respectively. The 1-year, 2-year, and 3-year survivals for the entire group were 67.9%, 38.7%, and 27.8%, respectively. In summary, brachytherapy offers a useful surgical approach in patients in whom unresectable pulmonary or mediastinal malignancies are found at the time of thoracotomy or in patients previously treated with other modalities for whom limited therapeutic alternatives exist.