A review of the respiratory effects of smoking cocaine.

A variety of pulmonary complications related to the use of freebase cocaine have been reported in the medical literature. Pulmonary barotrauma, hypersensitivity pneumonitis, pulmonary hemorrhage, obliterative bronchiolitis, asthma, and pulmonary edema have all recently been described. The number of reports are few, reflecting either the low incidence of these complications or the lack of recognition of these phenomena as cocaine-related illnesses. The mechanism by which freebase cocaine can injure the lung is not well defined. Whether an abnormal immunologic response to cocaine freebase can result in hemorrhage, pneumonitis, bronchiolitis, or asthma remains speculative. Whether cardiogenic or non-cardiogenic factors play a role in the development of pulmonary edema in freebase smokers has not yet been determined. Likewise, the roles of either cocaine, tobacco, or adulterants in producing the observed abnormalities of lung function remain controversial. Further reporting of freebase-related pulmonary complications, as well as the development of appropriate animal models, is needed.

Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.

PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension.

Pericardial effusion was noted in 43 of 79 patients (54%) with severe primary pulmonary hypertension. Larger effusion was associated with hemodynamic and echocardiographic evidence of right heart failure, impaired exercise tolerance, and a poor 1-year prognosis.

Nephrobronchial fistula and lung abscess resulting from nephrolithiasis and pyelonephritis.

There are multiple etiologies reported as causes of lung abscess; however, this differential rarely includes intra-abdominal abnormalities other than extension of a hepatic process. We describe a patient who was found to have a lung abscess and empyema resulting from the development of a nephrobronchial fistula secondary to nephrolithiasis and pyelonephritis. The patient had no urinary symptoms or known abdominopelvic infection and the etiology of lung abscess was only incidentally discovered after chest CT revealed extension of pleural fluid below the diaphragm.

The role of transbronchial lung biopsy in the treatment of lung transplant recipients. An analysis of 200 consecutive procedures.

STUDY OBJECTIVE: The purposes of this study were as follows: (1) to establish the positivity rate and complication rate of transbronchial lung biopsies in the treatment of lung transplant recipients; (2) to determine the sensitivity of transbronchial lung biopsy specimens for the diagnosis of clinically suspected acute rejection and cytomegalovirus pneumonia; and (3) to examine the results of surveillance transbronchial lung biopsies in clinically and physiologically stable recipients. DESIGN: Retrospective review and analysis of 203 consecutive procedures. SETTING: Washington University Lung Transplantation Program, Washington University School of Medicine and Barnes Hospital, St. Louis, Mo. PATIENTS: Fifty-five lung transplant recipients. INTERVENTIONS: Biopsies were done with 2-mm fenestrated forceps using fluoroscopic guidance. Two hundred three bronchoscopies with transbronchial lung biopsy were performed for clinical indications (n = 88), routine surveillance (n = 90), or follow-up of a previous biopsy (n = 25). Biopsy specimens showing acute allograft rejection were classified according to the scheme recommended by the Lung Rejection Study Group. MEASUREMENTS AND RESULTS: The positivity rate and complication rate were determined for the procedures. In procedures performed for clinical indications, the sensitivity for the diagnosis of acute rejection and cytomegalovirus pneumonia was calculated by a decision-to-treat analysis. A specific histologic diagnosis was detected in 69 percent of the clinical procedures, 57 percent of the surveillance procedures, and 64 percent of the follow-up procedures. For clinical indications, the sensitivity of transbronchial lung biopsy was 72 percent for the diagnosis of acute rejection and 91 percent for the diagnosis of cytomegalovirus pneumonia. Surveillance biopsy specimens often showed clinically inapparent rejection or cytomegalovirus pneumonia. The overall complication rate was 8.9 percent; none of the complications were life threatening. CONCLUSIONS: Transbronchial lung biopsy is a useful and safe procedure in the treatment of lung transplant recipients. When performed for clinical indications, the procedure proved to be sensitive for the diagnosis of acute rejection and cytomegalovirus pneumonia. When performed for surveillance in clinically and physiologically stable recipients, the incidence of rejection and cytomegalovirus pneumonia was unexpectedly high; the potential clinical implications of these findings will require further study.

Lung transplantation of ventilator-dependent patients. The Washington University Lung Transplantation Group.

During the last few years, lung transplantation has been extended to patients with a variety of end-stage lung diseases, but recipient selection guidelines have remained relatively strict. Ventilator-dependent patients have traditionally been considered poor candidates for transplantation. However, patients who have been thoroughly evaluated and accepted for transplantation and subsequently develop respiratory failure caused by progression and/or exacerbation of their underlying disease and recipients who experience respiratory failure caused by graft failure may be suitable candidates while ventilator-dependent if no other major complications or contraindications arise before a donor organ becomes available.

Lung transplantation. Analysis of thirty-six consecutive procedures performed over a twelve-month period. The Washington University Lung Transplant Group.

A consecutive series of 36 lung transplant procedures in 35 patients, performed over a 12-month period, has been reviewed. There were 14 men and 21 women undergoing 23 single, 12 bilateral, and one en bloc double lung transplant. There were one hospital death and three late deaths in the series, giving a hospital survival rate of 97.2% and a 1-year actuarial survival figure of 91.7%. Airway complications occurred in six patients (17.2%), one of whom died. Cytomegalovirus infection was demonstrated in 18 patients (51%), but no deaths have resulted. The most common cardiac complication was an atrial tachyarrhythmia (nine patients, 25.7%) and three patients had a cardiac arrest, but all were successfully resuscitated. Twelve patients required a further 25 surgical procedures after transplantation; however, renal and hematologic complications were uncommon. The prevalence and management of the other associated complications is discussed.

Pulmonary complications of liver transplantation.

The preoperative pulmonary evaluation of organ transplant candidates involves the diagnosis of unexplained pulmonary infiltrates or symptoms, interpretation of pulmonary function abnormalities, and an assessment of surgical risk. Pretransplant pulmonary considerations in patients with end-stage hepatic diseases relate primarily to hypoxemia from poorly understood intrapulmonary vascular dilatations, mechanical dysfunction, and states of increased extravascular lung water. Except in severe cases, however, these generally do not prohibit liver transplantation, and even are likely to improve after transplant surgery. Early postoperative complications may be categorized as those expected from extensive intra-abdominal surgery that requires significant volume resuscitation, which typically are managed in the usual manner for those clinical situations. As immunosuppression begins to have an effect, the LTx recipient becomes susceptible to the same opportunistic infectious organisms (with their frequent pulmonary involvement) that cause significant morbidity and mortality in recipients of other solid organ transplants. Because many of the immunosuppressive agents also are the same, noninfectious side effects such as pulmonary edema and malignancy also are similar. As with all immunocompromised patients, prophylaxis, when possible, persistent infection surveillance, and an aggressive diagnostic and therapeutic approach help decrease the impact of pulmonary dysfunction in LTx recipients.

Pneumocystis carinii pneumonia: advances in diagnosis and therapy.

As the AIDS epidemic has evolved, so have improvements been made in diagnosis and treatment of Pneumocystis carinii pneumonia, the most common opportunistic infection in AIDS. Advances, changes, and current research are discussed.

Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection.

Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH-; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analyzed for association with DTH+/- status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P=0.005; 95% CI=1.28-3.97) and TGFBI (OR 1.94; P=0.003; 95% CI=1.24-3.03). VL child/parent trios gave no evidence of association, but the DTH- phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P=0.006; 95% CI=1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P=0.042; 95% CI=1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil.

Invasive diagnostic approaches to pulmonary infiltrates.

The clinical and radiographic presentation of pulmonary disease in organ-transplant recipients often fails to allow the specific identification of a causative pathogen or permit the distinction between infectious and noninfectious processes. Frequently, invasive procedures are required to make a specific diagnosis and initiate appropriate therapy. The early use of transtracheal aspiration proved useful for the diagnosis of bacterial and mycobacterial pneumonias. However, its inability to reliably prove pneumonia caused by opportunistic pathogens, such as Pneumocystis carinii and cytomegalovirus, led to very narrow indications for its use among organ-transplant recipients. The introduction of fiberoptic bronchoscopy in the 1970s, with its large variety of related procedures, revolutionized the approach to the diagnosis of pulmonary disease among immunosuppressed patients and today remains the initial procedure of choice in the majority of clinical situations. The diagnostic success and relatively low morbidity of bronchoscopy has narrowed the indications for surgical lung biopsy, despite its excellent diagnostic yield. Open or thoracoscopic lung biopsies are most often used where bronchoscopy has failed to make a diagnosis or where the risk of bleeding prohibits a bronchoscopic biopsy.

Which patients are candidates for lung transplantation? Indications for unilateral, bilateral, and heart-lung procedures.

Single-lung transplantation, long successful in resolving interstitial lung disease, can now be used in COPD patients and shows promise in managing pulmonary hypertension. The bilateral procedure, which often avoids cardiopulmonary bypass, is preferred when chronic airway infection is present. Heart-lung transplants, now rare, are used when pulmonary hypertension is complicated by congestive cardiomyopathy or irreparable cardiac defects. Mechanical ventilation, prior cardiothoracic surgery, and corticosteroid use no longer constitute absolute contraindications to lung transplantation. The growing scarcity of donor organs is increasing waiting times; thus, earlier recognition of potential recipients is necessary.

Safety and yield of transbronchial biopsy in mechanically ventilated patients.

OBJECTIVE: To evaluate the safety and diagnostic yield of transbronchial biopsy performed in mechanically ventilated patients. DESIGN: Retrospective, cohort analysis. SETTING: A university-affiliated teaching hospital. PATIENTS: Seventy-one consecutive, mechanically ventilated patients requiring lung tissue examination. INTERVENTIONS: Transbronchial lung biopsy. MEASUREMENTS AND MAIN RESULTS: We evaluated complications associated with transbronchial biopsy, diagnostic yield of the procedure, and changes in patient management based on the results of the transbronchial lung biopsies. Eighty-three transbronchial lung biopsy procedures were performed in this patient cohort. Complications associated with these procedures included the following: ten (14.3%) pneumothoraces in patients without preexisting chest tubes; five (6.0%) episodes of bronchial hemorrhage of > 30 mL; transient oxygen desaturation to < 90% in seven (8.4%) patients; hypotension with a mean arterial pressure of < 60 mm Hg in six (7.2%) patients; and three (3.6%) episodes of tachycardia, with a heart rate of > 140 beats/min. No patient deaths, episodes of pneumonia, or sepsis could be attributed to the transbronchial lung biopsy procedures. Specific histologic diagnoses were made with 29 (34.9%) of the transbronchial biopsies, and patient management was changed as a direct result of the lung tissue examination in 34 (41.0%) instances. Pathologic correlation between the transbronchial biopsy specimens and lung tissue obtained by open-lung biopsy or post mortem examination occurred in 11 (84.6%) of 13 paired samples. CONCLUSION: Transbronchial lung biopsy can be performed with an acceptable risk and reasonable diagnostic yield in certain types of mechanically ventilated patients, often obviating the need to perform open-lung biopsy.

The Washington University-Barnes Hospital experience with lung transplantation. Washington University Lung Transplantation Group.

OBJECTIVE: --To review our experience with lung transplantation, emphasizing recipient selection, choice of procedure, functional results, and outcome. DESIGN: --Retrospective review of patients who received lung transplants at Barnes Hospital, St Louis, Mo, between July 1, 1988, and January 31, 1991. SETTING: --Washington University School of Medicine, St Louis, Mo, and Barnes Hospital, a medical school and its affiliated referral hospital, respectively. PATIENTS: --Sixty-nine lung transplant procedures were performed in 66 recipients. Patients with clinically and physiologically severe lung disease were selected according to predetermined guidelines. Underlying diseases in the recipients included chronic obstructive pulmonary disease, alpha 1-antitrypsin deficiency emphysema, cystic fibrosis, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome associated with an atrial septal defect, bronchiectasis, eosinophilic granuloma, and lymphangiomyomatosis. INTERVENTION: --Double-lung, bilateral sequential, and single-lung transplantations were performed. Eight patients underwent en bloc double-lung transplantations or a modification of this procedure with separate bronchial anastomoses. Thereafter, the bilateral sequential approach to replacement of both lungs was performed in 26 patients. Thirty-two patients underwent single-lung transplantations. MAIN OUTCOME MEASURES: --Pulmonary function tests, arterial blood gas levels, pulmonary artery pressure, pulmonary vascular resistance, and actuarial survival. RESULTS: --Actuarial survival at 1 year for the 66 lung transplant recipients was 79%. Actuarial survival at 1 year was 82% for the bilateral lung transplant recipients and was 90% for the single-lung transplant recipients. In patients with either restrictive or obstructive lung disease, pulmonary function tests and arterial blood gas levels improved markedly after lung transplantation. In patients with primary pulmonary hypertension or Eisenmenger's syndrome, the pulmonary artery pressure decreased and the cardiac index increased into the normal range after single-lung transplantation. CONCLUSIONS: --In carefully selected patients with end-stage lung disease, single-lung and bilateral lung transplantations can significantly improve functional capacity, with promising early actuarial survival statistics after 1 year.

Cytomegalovirus pneumonia: the use of ganciclovir in marrow transplant recipients.

Sixteen bone marrow transplant recipients with cytomegalovirus pneumonia diagnosed by rapid, non-invasive methods were treated with ganciclovir. Seven patients survived the acute infection and there were five long term survivors. Excellent in-vivo suppression of cytomegalovirus was observed. Marrow toxicity was noted in four patients but was rapidly reversible and not life threatening. Clinical features common to surviving patients included good clinical condition, insidious development of infection and evidence of normal alveolar gas exchange. The fulminant onset of symptoms, radiographic abnormalities and hypoxaemia were characteristic of non-survivors. These results offer some encouragement towards further study of ganciclovir for the early treatment of cytomegalovirus pneumonia. To identify such patients, the use of rapid diagnostic methods and aggressive viral surveillance is recommended. Convincing evidence for the efficacy of this drug will only emerge from randomized prospective studies.

Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants.

In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV-seronegative lung transplant recipients of organs from seropositive donors (D+/R-) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10-21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R- patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P = .023 and P = .021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients.

Comparison of PCR and pp65 antigenemia assay with quantitative shell vial culture for detection of cytomegalovirus in blood leukocytes from solid-organ transplant recipients.

This study compared PCR and an assay for cytomegalovirus (CMV) pp65 antigenemia (CMV-vue; INCSTAR Corp.) with a quantitative shell vial culture (QSVC) technique for the detection of CMV in serial blood specimens from 46 solid-organ transplant recipients. In a comparison based on 535 specimens tested by PCR and QSVC, CMV was detected by PCR in 41 and by QSVC in 37 of 43 recipients at risk of CMV infection. The mean number of days after transplantation of initial detection of CMV was 29.9 for PCR and 34.0 for QSVC (P = 0.01). The antigenemia assay was performed on 395 specimens, including 304 of those also tested by PCR. In these specimens, CMV was detected by the antigenemia assay, QSVC, and PCR in 30, 32, and 35 (respectively) of 38 patients at risk, with no statistically significant difference in the time to detection. Each of the assays detected CMV in similar proportions of patients with and without clinically significant CMV infection. PCR stayed positive longer after transplantation than the other assays but frequently returned to negative when more than 6 months had elapsed after transplantation. The antigenemia assay and PCR stayed positive longer after institution of antiviral therapy than QSVC. PCR can provide highly sensitive detection of CMV viremia, but a PCR assay for CMV is not yet available in kit form. The pp65 antigenemia assay and shell vial culture are quantifiable and comparable in sensitivity. Either is recommended for rapid detection of CMV in blood specimens from solid-organ transplant recipients.

Quantitative cultures of the cell fraction and supernatant of bronchoalveolar lavage fluid for the diagnosis of cytomegalovirus pneumonitis in lung transplant recipients.

Results of quantitative shell vial cultures of cell and supernatant fractions of bronchoalveolar lavage (BAL) fluid from lung transplant recipients were compared with results of transbronchial lung biopsies. Cytomegalovirus (CMV) was present in both the cell and supernatant fractions, including 28 (80%) and 29 (83%), respectively, of 35 BAL samples with corresponding biopsies that showed evidence of CMV pneumonitis and 34 (15%) and 75 (33%), respectively, of 227 BAL samples with corresponding biopsies that did not. Cultures of unseparated BAL fluid had a similar yield to cultures of supernatant. Virus titers of cell fractions and supernatants from BAL samples with corresponding biopsies that were positive for CMV pneumonitis were higher than those from BALs with negative corresponding biopsies. Culture of the unseparated fluid is recommended for simplicity and to maximize detection of CMV. Quantitative results may help in the identification of CMV pneumonitis, but additional studies are needed before quantitative cultures can be recommended for routine use.

Cytomegalovirus infection and pneumonitis. Impact after isolated lung transplantation. Washington University Lung Transplant Group.

Using aggressive surveillance of blood, bronchoalveolar lavage (BAL) fluid, and lung tissue, we sought to determine the incidence of cytomegalovirus (CMV) pneumonitis in isolated lung transplant recipients and to characterize its impact on pulmonary function, chronic rejection, and survival. Forty-six lung transplant recipients who survived greater than 30 days had prospective documentation of CMV infection in blood and BAL fluid and regular surveillance with transbronchial lung biopsy. CMV infection was documented in 92% of patients who were D-/R+, D+/R+, or D+/R-, and the incidence of histologically confirmed CMV pneumonitis among these patients was 75%. No D-/R- patient experienced CMV infection or disease. D+/R- patients experienced more frequent and severe episodes, and ganciclovir prophylaxis during the first 2 wk was not useful. CMV pneumonitis was accompanied by detectable radiographic changes in less than one third of cases. The detection of CMV in BAL fluid was not predictive of CMV pneumonitis on biopsy, except in D+/R- patients during the first 90 days after transplantation. There was no evidence of an adverse impact because of CMV infection on pulmonary function during the first year after transplantation. A relationship between CMV infection and bronchiolitis obliterans could not be documented; however, D+/R- patients had higher morbidity and a trend toward lower survival. In a multivariate analysis, D+/R- status was an independent predictor of death.

Use of a modified shell vial technique to quantitate cytomegalovirus viremia in a population of solid-organ transplant recipients.

A quantitative modification of the shell vial assay was used to investigate cytomegalovirus viremia in solid-organ transplant recipients. The level of viremia detected in 109 of 407 specimens ranged from 0.02 to 28 infectious foci per 100,000 leukocytes. By using a Poisson model, a technique was developed to determine 95% confidence limits for the measured levels of viremia. These confidence limits were used to determine the level of viremia that could be excluded by culturing a given number of cells. Longitudinal assessment of two transplant recipients revealed different patterns of viremia and demonstrated that significant disease sometimes occurred with low-level viremia. On the basis of the results of the studies, culture of at least 4 x 10(6) leukocytes is recommended for the sensitive detection of cytomegalovirus viremia.