Gastroesophageal Reflux and Microaspiration in Lung Transplant Recipients: The Utility of a Single Esophageal Manometry and pH Probe Monitoring Study.

BACKGROUND: Gastroesophageal reflux (GER) in recipients of lung transplant (LTX) is associated with chronic allograft rejection, presumably via microaspiration that damages airway epithelium. Most LTX programs perform a single post-LTX esophageal study to evaluate for GER; the efficacy of this test is unclear. METHODS: Patients with 1 year of post-LTX follow-up, including routine bronchoscopies with bronchoalveolar lavage fluid (BALF) samples as well as high-resolution esophageal manometry and pH probe monitoring (HREMpH), were evaluated. BALF samples were analyzed with competitive enzyme-linked immunosorbent assay to detect bile salts, which are indicative of aspiration. These results were compared to results of HREMpH studies post LTX. RESULTS: Ninety BALF samples were analyzed for bile salts and acted as disease positive for this evaluation. Of the 13 HREMpH cases, 8 were positive for GER, but only 3 were positive for bile salts via assay. Of the 5 HREMpH-negative cases, 2 experienced aspiration. A solitary HREMpH study had 60.0% sensitivity and 37.5% specificity with positive and negative likelihood ratios: 0.96 and 1.07, respectively. CONCLUSION: Microaspiration appears to be an intermittent phenomenon, and HREMpH screening poorly correlates with BALF evidence of aspiration; which may not be adequate. As aspiration detection is crucial in this population, further analysis is warranted.

Mortality associated with Acinetobacter baumannii infections experienced by lung transplant recipients.

Lung transplantation (LTX) requires continual systemic immunosuppression, which can result in infections that may compromise recipient survival. A recent outbreak of Acinetobacter baumannii at our institution resulted in infections experienced in both LTX recipients and nontransplant patients. A retrospective review was conducted of patients who had A. baumannii recovered from blood, other normally sterile body fluids, and/or respiratory secretions and who had clinical follow-up extending to 1 year postinfection. A. baumannii was considered "multidrug-resistant" when its growth was not inhibited by minimum inhibitory concentrations of multiple antibiotics. Despite the resistance profile, patients were treated with a combination of antibiotics, which included tigecycline, colistimethate, and when susceptible, imipenem. Once infection was diagnosed, immunosuppression was reduced in all LTX recipients. Six LTX recipients became infected with A. baumannii and were contrasted to infections identified in 14 non-LTX, nonimmunosuppressed patients. A. baumannii was persistently recovered in 4 of 6 LTX recipients (66.7%) compared with only 1 of 14 (7.1%) non-LTX patients (χ(2) = 9.9, p = 0.005). LTX recipients received antibiotic therapy for an average of 76 ± 18.4 days compared with 16.0 ± 6.8 days for the non-LTX patients (p = 0.025, Mann-Whitney U test). All 4 of the 6 (66.7%) LTX recipients died as a consequence of their infection compared with 1 of 14 (7.1%) of the non-LTX patients (χ(2) = 9.9, p = 0.005). Despite receiving more antibiotic therapy, LTX recipients who were infected with multidrug-resistant A. baumannii were less likely to clear their infection and experienced greater mortality compared with non-LTX patients.

Neutrophils, unopposed neutrophil elastase, and alpha1-antiprotease defenses following human lung transplantation.

Neutrophils are sequestered in the newly transplanted lung after reperfusion or with infection, rejection, and chronic graft dysfunction. Because unopposed (free) neutrophil elastase (NE) released into bronchoalveolar secretions may injure the lung allograft and impair bacterial clearance, we assessed total neutrophil numbers, myeloperoxidase activity as an index of neutrophil influx and degranulation, alpha1-antiprotease (alpha1-AP) concentrations, and unopposed NE activity in bronchoalveolar secretions from lung transplant recipients. Unopposed NE activity was present in bronchoalveolar lavage fluid (BALF) from recipients transplanted for emphysema associated with alpha1-AP deficiency as well as recipients without such deficiency (171 of 2,137 BALF; 8%). Ten of 17 (59%) recipients with alpha1-AP deficiency who were followed for at least 1 yr after transplant with multiple surveillance and diagnostic bronchoscopies had at least one BALF containing unopposed NE, usually associated with the presence of > or = 10(5) colony forming units/ml BALF of aerobic bacteria. In contrast, 19 of 58 (33%) with emphysema not associated with alpha1-AP deficiency, 8 of 32 (25%) recipients with cystic fibrosis (CF), 6 of 16 (38%) with idiopathic pulmonary fibrosis (IPF), and 11 of 36 (31%) with other indications for transplant had unopposed NE in BALF. alpha1-AP levels were significantly elevated in the early posttransplant time period and could be augmented considerably in alpha1-AP-deficient recipients with episodes of infection or rejection. Our findings indicate that unopposed NE activity can be found in both alpha1-AP-deficient and alpha1-AP-sufficient recipients after transplantation, usually in association with endobronchial bacterial infection.

Empyema complicating successful lung transplantation.

OBJECTIVE: To assess the prevalence and etiology of empyema complicating successful lung transplantation. DESIGN: Retrospective review. SETTING: University medical center transplant service. PATIENTS: All recipients (n = 392) of single-lung, double-lung, and heart-lung transplantation between May 1984 and April 1997. RESULTS: Of the 392 transplant recipients, empyema was documented in 14 patients (3.6%) at a mean time (+/- SD) of 46 days after transplantation (range, 14 to 167 days). Of these 14 recipients with empyema, 4 recipients (28.6%) died of infectious complications related to empyema. Empyema was seen secondary to Gram-positive, Gram-negative, and saprophytic organisms; however, there was no predominance of a particular organism recovered from the empyemic fluid (chi2 = 0.53; p = 0.75). The development of empyema was not related to whether the transplant was performed secondary to a septic or nonseptic lung disorder (chi2 = 1.06; p = 0.67), nor was it related to the type of transplant procedure performed (ie, single-lung, double-lung, or heart-lung allografts; chi2 = 4.39; p = 0.30). CONCLUSION: Empyema, a relatively uncommon complication of lung transplantation, is not related to the type of allograft received or to whether the recipient had a septic or a nonseptic lung disorder. If empyema does occur, the mortality associated with this infection is substantial.

Lung transplantation for end-stage pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is a multi-system granulomatous disease which can cause significant pulmonary morbidity and occasionally be fatal. The long term benefit of lung transplantation for this disorder are unknown. METHODS: A retrospective review was made of nine single lung transplant procedures performed at the University of Pittsburgh between March 1991 and March 1995 in patients with end-stage lung disease secondary to sarcoidosis. Two contemporaneous groups of recipients receiving transplants for COPD (n = 30) and inflammatory lung disease (n = 13) served as control groups. Surviving recipients underwent sequential surveillance bronchoscopy with transbronchial biopsy. RESULTS: All recipients survived beyond post-operative day (POD) 30, with 5 recipients currently alive. One year survival for this group was 6/9 (67%). Eight of the 9 sarcoidosis recipients had sequential lung biopsy procedures. Five of these 8 recipients (62.5%) had recurrence of granulomata in the lung allograft with the mean time to diagnosis of recurrent sarcoidosis being POD 224.2 +/- 291.3 (range POD 21-719). None of these 5 recipients had radiographic evidence or clinical symptoms related to granulomatous inflammation in the allograft. Pre-operative and post-operative spirometric values were available on 8 recipients. Vital capacity significantly improved in all recipients from 1.54 +/- 0.43 litres to 2.55 +/- 0.63 litres by POD 180 and was maintained through the fourth postoperative year (p < 0.05 Wilcoxon Signed Rank). Spirometric values were also compared before and after transplantation in the 5 recipients with granulomata in the allograft. Vital capacity significantly improved in these 5 recipients from 1.53 +/- 0.48 litres to 2.71 +/- 0.71 litres by POD 180 and was maintained throughout the first postoperative year (p < 0.05, Wilcoxon Signed Rank). The prevalence of high grade acute cellular rejection [ACR (histologic grades III and IV)] did not differ from that seen in a contemporaneous group of 30 single lung recipients who received allografts for COPD (p < 0.05 Mann-Whitney U), nor when compared to a group of 13 single lung recipients who received allografts for immunologically mediated lung disease (p < 0.05 Mann-Whitney U). The prevalence of chronic rejection (histologic obliterative bronchiolitis [OB]) in the sarcoidosis recipients was 4/8 (50%). In the controls with COPD recipients the prevalence of OB was 10/30 (33.3%), and in the 13 controls with immunologic disease it was 6/13 (46.2%). There was no significant difference in the prevalence of OB between the sarcoidosis recipients and controls. When analyzed to the fifth year after transplantation, freedom from the development of OB also failed to differ between these 3 groups (p = 0.25, Logrank, Mantel-Cox). CONCLUSIONS: Although granulomatous inflammation in the lung allograft is common following transplantation for sarcoidosis, it is not clinically or radiographically relevant. In addition, the prevalence of high grade ACR and histologic OB is no different when compared to other single lung recipients. For these reasons lung transplantation is a viable alternative for end-stage lung disease secondary to sarcoidosis.

Unopposed neutrophil elastase in bronchoalveolar lavage from transplant recipients with cystic fibrosis.

Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteolytic activity are found in lower respiratory tract secretions from most patients with advanced cystic fibrosis (CF). To determine whether antielastase defenses may be overwhelmed in epithelial lining fluid after lung transplantation, we measured NE activity (cleavage of the specific substrate, MeO-Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained for surveillance or diagnostic purposes at various intervals (1 mo to 7 yr after transplantation) from 52 recipients who had undergone double or bilateral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had >= 10(5) colony forming units (cfu) of Pseudomonas aeruginosa in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had developed obliterative bronchiolitis (OB), but only 8 of the 38 subjects without unopposed NE activity had OB (p = 0. 002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF patients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE activity in BAL from lung allografts of patients with CF is associated with progressive, irreversible OB and graft failure.

Pulmonary aspergillosis in cystic fibrosis lung transplant recipients.

STUDY OBJECTIVE: To define the prevalence of colonization and infection of the lower respiratory tract (LRT) with Aspergillus in lung transplant recipients with and without cystic fibrosis (CF). DESIGN: Retrospective review. SETTING: Large university lung transplant center. MATERIALS AND METHODS: The postoperative course of 31 CF and 53 non-CF double lung or double lobar transplant recipients receiving allografts from April 1991 to February 1996 was reviewed. All recipients were subjected to surveillance bronchoscopy and biopsy at predetermined intervals and when clinically indicated. BAL fluid (BALF) and biopsy material were examined by appropriate fungal culture and staining techniques. Infection was defined by the finding of tissue-invasive disease on biopsy specimens. RESULTS: Seven of the 31 CF recipients (22%) had Aspergillus isolated from cultures of sputum prior to transplantation. Following transplantation, 15 CF recipients (48%) had Aspergillus isolated from either sputum or BALF, including 4 of the 7 recipients identified with the fungus prior to transplantation. By contrast, 21 of the 53 non-CF recipients (40%) had Aspergillus isolated from the LRT following transplantation, none having had the fungus isolated prior to transplantation. The prevalence of Aspergillus did not differ between these groups (p = 0.51). Infections with Aspergillus occurred in 4 of the CF recipients (27%) and did not differ from the 3 infections (14%) identified in the non-CF recipients (p = 0.36). However, three of the four infections in the CF recipients involved the healing bronchial anastomosis and occurred prior to postoperative day 60. All three of these recipients had Aspergillus preoperatively. Postoperative infection was more common in the CF recipients having Aspergillus preoperatively than in those CF recipients without preoperative Aspergillus (p = 0.02). CONCLUSIONS: Isolation of Aspergillus from the LRT following double lung transplantation is common and generally not associated with tissue-invasive disease. Those CF recipients with Aspergillus isolated in cultures of sputum preoperatively are at risk for postoperative infections with this agent. The healing bronchial anastomosis is particularly vulnerable.

Allograft colonization and infections with pseudomonas in cystic fibrosis lung transplant recipients.

OBJECTIVE: To assess the incidence of pseudomonal infection, colonization, and inflammation in the allograft of lung transplant recipients with cystic fibrosis (CF) as compared with recipients with other end-stage lung disease. DESIGN: Retrospective review. SETTING: University medical center transplant service. PATIENTS: All patients with CF and chronic pseudomonal infection (n=62) and patients with nonseptic end-stage lung disease (n=52) receiving a double lung transplant between October 1983 and March 1996. RESULTS: Fifty lung transplant recipients with CF survived beyond postoperative day (POD) 15 and were subject to sequential bronchoscopy with BAL. Forty-four CF lung transplant recipients had Pseudomonas isolated from the allograft by median POD 15 as compared with 21 non-CF lung transplant recipients (p<0.001) with isolation at median POD 158 (p<0.0001). Thirteen CF lung transplant recipients had histologic evidence of infection when Pseudomonas was isolated as compared with only three of the non-CF lung transplant recipients (p<0.01). These infections occurred earlier in the CF lung transplant recipients (median POD 10 vs 261) (p<0.01). When compared with non-CF lung transplant recipients, CF lung transplant recipients with Pseudomonas isolated but without concomitant histologic infection (colonized) were demonstrated to have increased number of polymorphonuclear cells (PMNs) in the BAL fluid recovered from the allograft (17.66+/-24.94 x 10(6) cells vs 3.46+/-4.73 x 10(6)) (p<0.05). Non-CF lung transplant recipients who became colonized with Pseudomonas also had a greater number of PMNs recovered when compared with non-CF lung transplant recipients who did not have Pseudomonas (22.32+/-34.00 x 10(6) cells vs 0.21+/-0.18 x 10(6)) (p<0.01). Nine of 32 (28%) lung transplant recipients with CF have died from pseudomonal allograft infections, but this is no greater than 4 of 21 (19%) deaths related to Pseudomonas infection in recipients without CF (p=0.34). CONCLUSIONS: Isolation of Pseudomonas from the lung allograft occurs more frequently and earlier after transplantation in recipients with CF. While infections related to Pseudomonas also occur more frequently in recipients with CF, there is no increase in mortality. There is an intense inflammatory response in the lung allograft associated with the isolation of Pseudomonas in recipients with and without CF.

Human sequelae of severe carbamate poisoning.

Carbofuran is a carbamate that functions as a cholinesterase inhibitor. Accidental or intentional ingestion can produce a life-threatening syndrome that requires prompt diagnosis and treatment. We describe a case of intentional carbofuran ingestion that resulted in coma, respiratory failure from acute respiratory distress syndrome (ARDS), and cortical blindness.

Use of aerosolized colistin sodium in cystic fibrosis patients awaiting lung transplantation.

BACKGROUND: In patients with cystic fibrosis (CF) who are awaiting lung transplant, prolonged exposure to systemic antibiotics has frequently led to airway colonization with resistant isolates of Pseudomonas. This resistance limits the arsenal of effective antimicrobials available for infections after the initiation of immunosuppression and has been considered a theoretical deterrent to lung transplantation. METHODS: Twenty CF transplant candidates with "pan-resistant" Pseudomonas received maintenance antibiotic therapy with aerosolized colistin sodium (75 mg b.i.d.), and intravenous antibiotics were eliminated. Ten other CF candidates did not use colistin sodium. Sputum cultures and antibiotic sensitivities were followed every 3-6 weeks. RESULTS: All 20 candidates (100%) who used aerosolized colistin sodium became colonized with sensitive isolates of Pseudomonas in an average of 45.1+/-20.2 days. In contrast, only 3 of 10 CF transplant candidates (30%) who did not use colistin sodium later became colonized with sensitive isolates. The mean time to spontaneous emergence of sensitive organisms was 144.6+/-48.0 days in candidates who did not use colistin sodium and was significantly longer than in the candidates who used colistin sodium (P=0.007). The occurrence of redeveloping sensitive isolates of Pseudomonas was significantly greater in the candidates who used colistin sodium (P<0.05). Of the candidates who used colistin sodium, six have been transplanted at our institution. In five of these six recipients (83.3%) bacterial cultures taken from the explanted lungs continued to demonstrate sensitive organisms. CONCLUSION: Aerosolized colistin sodium may be a useful therapy to promote emergence of sensitive microbes in CF candidates with pan-resistant isolates of Pseudomonas.

Spirometry values in stable lung transplant recipients.

To clarify the usefulness of spirometry to assess the function of the lung allograft post-transplant, we retrospectively reviewed 351 sequential spirometry measurements performed by 65 healthy recipients after the 80th postoperative day when the clinical evaluation and fiberoptic bronchoscopy with transbronchial biopsies and bronchoalveolar lavage excluded significant rejection or infection in the allograft. The mean coefficients of variation (CV) and significant values for change (SC) for the FVC, FEV1, and FEF25-75% were calculated according to the type of transplant procedure (heart-lung and double-lung [HL-DL] versus single-lung [SL]), and to the time after transplant when the spirometry measurements were obtained < or = 1 yr versus > 1 yr). The SC for the FVC decreased with time after transplantation for both HL-DL (< or = 1 yr: 17% versus > 1 yr: 7%) and SL recipients (< or = 1 yr: 13% versus > 1 yr: 8%). The higher degree of variability within the first year was primarily due to increasing values especially in the HL-DL recipients. The SC for the FEV1 also decreased over time for HL-DL recipients (< or = 1 yr: 18% versus > 1 yr: 9%) but was similar for SL recipients at both intervals (13%). Our results suggest that decreases of > or = 11% in FVC or 12% in FEV1 in HL-DL recipients and > or = 12% in FVC or 13% in FEV1 for SL recipients indicate a significant decrease in allograft function that may be due to infection or rejection.

Lung transplantation: implications for the general internist.

The modern era of lung transplantation was ushered in on the wings of discoveries in new immunosuppressive agents and surgical technique. It has allowed those with end-stage organ disease to have a second chance at life. Even though still in its youth relative to other solid organ transplants, it is gaining momentum and promises to be a continuing area of growth and development. Although over 2,700 lung transplants have been done in the last 13 years worldwide, the lack of availability of donor organs is the major factor slowing the rapid expansion of this field of endeavor. Primary care physicians may have an impact on this problem by raising the awareness for organ donation in their patients and patients' families. Although initially performed almost exclusively for those with pulmonary vascular disease, indications have now expanded to include interstitial disease, septic lung disease, and emphysema, with the latter being the major reason for transplantation today. Unfortunately, at experienced institutions with long waiting lists, 20% or more of candidates do not survive to transplantation. With proper care and selection of transplant candidates it is hoped that more will survive to benefit from this treatment. The primary care physician will likely be assuming a greater role in the management of transplant candidates as their numbers increase. The care of transplant recipients, although often complex, is frequently rewarding. For the most part it is performed at transplant centers, but a role for the recipient's local physician in this process is also growing in the era of managed care. This chapter has also highlighted how the recipient's local physician can participate in postoperative care. Strict attention needs to be paid to any and all signs of organ rejection or infection because both can have devastating consequences. Awareness of the medications used in this population, their side effects, and drug interactions is essential. Despite the recent advances in pharmacologic therapy, organ rejection continues to be problematic. This is especially the case with the entity of chronic rejection because it frequently fails to respond long-term to therapy and accounts for a significant percentage of late mortality. Although infections continue to be the primary cause of both early and late mortality in these recipients, proper care and postoperative prophylaxis can lessen the incidence. Likewise, early and aggressive treatment of infections in recipients can be lifesaving. Despite all the potential problems, patients receiving lung transplants are living longer and return to productive lives. Between 50% and 60% are now living between 3 and 4 years, and one can only anticipate that this will continue to climb as our understanding of infections, medications, and the body's immunoregulatory system improves. As techniques for donor organ allocation and organ preservation improve, it is hoped that all those with end-stage lung disorders may have the opportunity to benefit from this expanding technology.

Clinical trial of tacrolimus versus cyclosporine in lung transplantation.

BACKGROUND: A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation. METHODS: Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease. RESULTS: One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05). CONCLUSIONS: This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.

Endocarditis. Changing trends in epidemiology, clinical and microbiologic spectrum.

Infective endocarditis refers to infection of the endocardium or heart valves by microbes, resulting in tissue destruction. Clinical presentation is quite variable, and a high level of suspicion is essential for recognition. Diagnosis is dependent on identification of the causative agent in blood cultures. Cultures that are persistently negative indicate the presence of culture-negative endocarditis, and diagnosis is one of exclusion. Treatment of endocarditis consists of high doses of antibiotics active against the infecting organism. Individualized therapy is the key to management.

Aspergillus fumigatus sternal wound infections in patients undergoing open heart surgery.

During a 21-month period (July 1986-April 1988), six patients who underwent open heart surgery at Holston Valley Hospital and Medical Center in Kingsport, Tennessee, developed sternal would infections caused by Aspergillus fumigatus. All patients required sternectomy, reconstructive surgery, and long term amphotericin B therapy; no patient died. By univariate analysis, the following were significantly associated with A. fumigatus sternal would infection: chronic lung disease, a recent history of pneumonia, a greater mean number of admission diagnoses, and a particular surgeon. However, multivariate analysis identified chronic lung disease as the only independent risk factor and the best predictor of A. fumigatus sternal wound infections. No factors related to the surgical procedure or operating room personnel were associated with infection. A review of the characteristics of the patients undergoing open heart surgery showed that since 1985, there had been a trend for these patients at Holston Valley Hospital and Medical Center to be older and sicker, which may have contributed to the occurrence of infections never observed before. Despite an extensive investigation, no environmental source for A. fumigatus was identified. A. fumigatus, however, grew from the bronchial washing of one patient at the time the sternal wound infection was diagnosed, and a prospective study showed that the rate of A. fumigatus colonization among open heart surgery patients was the same as the rate of sternal wound infections caused by A. fumigatus. These data suggest that patients with chronic lung disease and respiratory colonization with A. fumigatus are at increased risk for A. fumigatus sternal wound infections after open heart surgery.

Percutaneous endoscopic gastrostomy as an unrecognized source of methicillin-resistant Staphylococcus aureus colonization.

Methicillin-resistant Staphylococcus aureus (MRSA) caused colonization or infection around the gastrostomy site of seven hospitalized patients, five of whom were in the long-term care unit. All cultures of gastrostomy sites were retrospectively reviewed, and 28% had MRSA. The gastrostomy site was responsible for 6.3% of all MRSA cultures, and 12.5% of all MRSA-positive patients with gastrostomy site cultures had involvement at that site. The implications of MRSA and gastrostomy tubes are discussed.

Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Comparison with interstitial lung disease and evaluation of the effect of intravenously administered antibiotic therapy.

In cystic fibrosis (CF), extracellular lung matrix is progressively damaged, neutrophils invade the air spaces, and activated neutrophils may release large amounts of neutrophil elastase (NE). Although alpha 1-antiprotease (alpha 1-AP) binds and inactivates NE and is the major antielastase of the lower respiratory tract, antielastase defenses may be overwhelmed in CF, leading to progressive lung damage. To determine whether the ability of alpha 1-AP to neutralize NE is impaired in CF, we compared NE activity in bronchoalveolar lavage (BAL) fluid and human neutrophil elastase/alpha 1-antiprotease (NE/alpha 1-AP) complex in both BAL fluid and peripheral blood serum from patients with CF, normal volunteers, and patients with interstitial lung disease. We detected a considerable amount of NE activity in BAL fluid from all but one patient with CF but none in that from normal volunteers or from patients with interstitial lung disease. Although in interstitial lung disease there was a significant correlation between increased NE/alpha 1-AP complex in BAL or peripheral blood and the degree of neutrophil influx, NE/alpha 1-AP complex was disproportionately low in CF BAL compared with significantly elevated values in serum. These data suggest that in CF, alpha 1-AP-mediated defense against free NE in the lower respiratory tract is significantly impaired, and high levels of uncomplexed, enzymatically active, NE are present in CF respiratory secretions. To determine whether intravenously administered antipseudomonal antibiotic therapy for exacerbations of CF lung disease diminished the amount of free NE in respiratory secretions, we used BAL to investigate the effect of such therapy on neutrophils and NE in patients with CF colonized with pseudomonads.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of pulmonary strongyloidiasis by bronchoalveolar lavage.

Bronchoalveolar lavage was performed on a patient with disseminated strongyloidiasis and 4.5 X 10(7) cells/65 ml of lavage fluid were recovered. Eighty-five percent of cells were polymorphonuclear leukocytes; 15 percent were pulmonary alveolar macrophages. Rhabditiform larvae (1 X 10(4)) were recovered in 65 ml of lavage fluid. This is the first report of bronchoalveolar lavage used in diagnosing disseminated strongyloidiasis.