Biomedical subjects

G I Snell

Publications and source records attributed to G I Snell.

At least 37 records · Page 2Linked to original sources

PubMed2000

Outcomes from paired single-lung transplants from the same donor.

BACKGROUND AND METHODS: Simultaneous, paired single-lung transplants from a single organ donor is one way to maximize lung transplant opportunities. Paired transplants allow comparison between left and right single-lung transplants and also provide insight into the relevance of donor vs recipient factors in rejection outcomes. RESULTS: Of 76 paired transplants (38 pairs) performed at the Alfred Hospital, 68 patients have survived >30 days. We observed no significant differences between left and right single-lung transplants in ICU stay (median, 3.1 vs 3.0 days; range, 0.5 to 83 vs 0.5 to 76 days), hospital stay (median, 19.5 vs 24.0 days; range, 1 to 118 vs 11 to 144 days), airway complications (5 vs 3), and 5-year survival (60% vs 50%). The 6 month, and 1- and 2-year survivals were lower in left single-lung transplant recipients, primarily related to increased mortality from airway complications. In 28 pairs, both recipients survived 90 days, and the incidence, frequency, and time of onset of acute rejection and chronic rejection (bronchiolitis obliterans syndrome [BOS]) were not significantly different. When sequentially performed lung transplants were separately analyzed, the incidence of acute rejection was not related to graft ischemic time. CONCLUSIONS: The general outcomes of right and left transplants are similar, although we observed increased 6-month to 2-year mortality associated with left lung transplantation. The lack of correlation between the incidence of acute rejection episodes or the severity of BOS in paired allograft recipients suggests that "donor factors" are not the dominant cause.

Adolescent↗

PubMed2000

Pharmacokinetic assessment of oral ganciclovir in lung transplant recipients with cystic fibrosis.

Oral ganciclovir has been used as prophylaxis and therapy against cytomegalovirus in patients with HIV infection and following organ transplantation. Oral ganciclovir has clear practical advantages over intravenous ganciclovir but has a relatively low bioavailability and this may be problematic in at-risk patients with malabsorption. The bioavailability and therefore therapeutic potential of oral ganciclovir in cystic fibrosis (CF) patients post-lung transplant (LT) might be expected to be inadequate given the high incidence of malabsorption in these patients. An 8 h pharmacokinetic study was performed in 12 CF patients 160 +/- 122 days post-transplant who had been taking 1 g oral ganciclovir tds for 3 days with food (plus normal enzyme supplements). Mean (range) serum creatinine was 150 Imol/L (70-280). Blood was sampled at 0.5, 1, 2, 3, 4, 6 and 8 h post-final dose. Plasma was stored at -20 degrees C and later analysed by highperformance liquid chromatography. Mean peak concentration (C(max)) was 4.8 mg/L (0. 96-12.8), mean minimum concentration (C(min)) was 3.6 mg/L (0.78-11. 7) and mean area under the curve (AUC) was 35.4 mg.8 h/L (8-99). C(max), C(min) and AUC correlated significantly with one another (P < 0.001) as well as with serum creatinine and creatinine clearance (P < 0.01). When corrected for alterations in renal function, plasma oral ganciclovir levels are as predicted for other transplant populations. Three days of oral ganciclovir results in therapeutically useful plasma drug levels in the CF LT population, despite a background of general malabsorption. C(max), C(min) and AUC are highly correlated, allowing for the possibility of steady-state drug monitoring to confirm that the recommended dosing algorithm produces appropriate plasma levels.

Adult↗

PubMed2000

Airway neutrophilia in stable and bronchiolitis obliterans syndrome patients following lung transplantation.

BACKGROUND: The bronchiolitis obliterans syndrome (BOS) remains the major constraint on the long term success of lung transplantation. Neutrophils have been associated with fibrosing lung conditions and have been noted to be increased in the bronchoalveolar lavage (BAL) fluid of patients with BOS. METHODS: This study was undertaken to examine neutrophil accumulation in the BAL fluid, airway wall and lung parenchyma, as well as levels of interleukin (IL)-8 in the BAL fluid, in normal controls and lung transplant recipients with and without BOS. Bronchoscopic examination included endobronchial biopsy (EBB), BAL fluid, and transbronchial biopsy (TBB) sampling. Tissue neutrophils were identified by neutrophil elastase staining on 3 microm paraffin biopsy sections and quantified by computerised image analyser. IL-8 levels were measured in unconcentrated BAL fluid by ELISA. RESULTS: Compared with controls, airway wall neutrophilia was increased in both stable lung transplant recipients and those with BOS (p<0.05). BAL neutrophils and IL-8 levels were also increased in both groups of transplant recipients compared with controls (p<0.01), the levels being significantly higher in the BOS group (p<0.01). Neutrophil numbers in the lung parenchyma were not significantly different between the two groups of lung transplant recipients. CONCLUSION: Increased levels of neutrophils are present in the airway wall and BAL fluid of lung transplant recipients with and without BOS. BAL fluid levels of IL-8 are also increased, raising the possibility that neutrophils and/or IL-8 may play a part in the pathogenesis of BOS following lung transplantation.

Adult↗

PubMed2000

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by increased exhaled nitric oxide levels and epithelial inducible nitric oxide synthase.

In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by airway inflammation and development of progressive airway narrowing and fibrosis. We have previously shown that in stable lung transplant recipients (LTR), mean eNO levels were not elevated but were still related to the degree of airway neutrophilia within the group. The hypothesis now tested is that in BOS, eNO levels are increased in association with even greater airway neutrophilia and enhanced expression of inducible (iNOS) nitric oxide synthase in the bronchial epithelium. We determined eNO levels in 40 LTR in four groups: well and "stable": LTR (n = 20), BOS (n = 8), bacterial airway infection (BI, n = 6), and acute rejection (AR, n = 6). Following bronchoscopic sampling, we performed a quantitative assessment of iNOS and constitutive nitric oxide synthase (cNOS) expression in endobronchial biopsies by immunohistochemistry. Mean +/- SEM eNO levels in BOS and BI were significantly higher than in stable LTR (20 +/- 1.2 parts per billion [ppb] and 24.7 +/- 1.7 ppb versus 12.5 +/- 0.9 ppb; p < 0.01 for both). In AR, eNO levels (13.4 ppb +/- 0.5) were not different in stable LTR (p = 0.34). When compared with stable LTR, there was increased expression of iNOS in the bronchial epithelium and generally in the lamina propria (LP) in patients with BOS and BI. In AR, iNOS expression was increased but only in the LP in a perivascular distribution. Expression of cNOS was reduced in BOS but not in BI and AR compared with the stable group. Using regression analysis, only iNOS expression in the bronchial epithelium (r(2) = 0.77; p < 0.0001) and %BAL neutrophils (r(2) = 0. 79; p < 0.0001) were positively related to eNO in stable LTR and BOS. We conclude that epithelial iNOS appears to be the major source of eNO. Exhaled NO levels also appear to reflect the degree of airway neutrophilia in both stable LTR and BOS groups. This suggests that serial eNO measurements may be able to predict the early development of BOS.

Acute Disease↗

PubMed1999

Impact of graft ischemic time on outcomes after bilateral sequential single-lung transplantation.

BACKGROUND: Graft ischemic time (GIT) is a potential limiting factor in lung transplantation. METHODS: Seventy-four patients who underwent bilateral sequential single-lung transplantation were divided into three groups: group I, GIT less than 5 hours (n = 20); group II, GIT between 5 and 8 hours (n = 39); and group III, GIT more than 8 hours (n = 15). We compared early allograft function (ratio of arterial oxygen tension to inspired oxygen fraction and alveolar-arterial oxygen gradient), blood loss, the need for tracheostomy, the duration of ventilation, intensive care unit stay, and hospital stay. We also compared prevalences of acute and chronic rejection, airway complications, lung function test, and 2-year survival. RESULTS: Early allograft function in group III was significantly worse than those in groups I and II. However, there was no significant difference in any other variables of early and medium-term outcomes among the three groups. No significant correlation was detected between GIT and duration of intensive care unit stay or hospital stay. CONCLUSIONS: The limitation of acceptable GIT could be extended from the traditionally approved 4 to 5 hours, to 5 to 8 hours or even longer.

Adult↗

PubMed1999

Airway vascular changes in lung allograft recipients.

BACKGROUND: In asthma there has been increasing interest in the contribution of airway microvasculature to airway wall thickness and lumenal narrowing. Post-lung transplant, the survival of the donor airway is generally dependent on mixed-venous blood flow from pulmonary artery collaterals associated with the discontinuation of the bronchial circulation. This may lead to an altered vasculature of the airways post transplant, which may contribute to airflow limitation. METHODS: Endobronchial biopsies were taken from the lower lobe sub-carinae in 22 lung transplant recipients (LTR), 8 with Bronchiolitis Obliterans Syndrome (BOS), 14 without, and 14 controls. Seven microm frozen sections were stained for type IV collagen with a monoclonal antibody, using an indirect immunoperoxidase method. Bronchial vessels were identified by typical staining of type IV collagen in the true basement membrane supporting the endothelium. The number of vessels per mm2 of submucosa to a depth of 150 microm below the basement membrane, the percent vascularity and average vessel size were quantified using a computerised image analyser. RESULTS: Compared to the controls, a higher percent vascularity was found in LTR both with and without BOS (p < 0.05). In the BOS group, the percent best FEV1.0 decreased exponentially, in association with increased airway vessel size (r2 = 0.67, p = 0.01). CONCLUSIONS: These findings suggest that increased airway vascularity is a feature of the allograft airways post transplant. This may be a result of the relative hypoxia and hypercarbia in the blood supplying the airways from the pulmonary artery collaterals or of the chronic inflammatory process in the airways. These changes in vascularity could contribute to airflow limitation in BOS.

Adult↗

PubMed1999

Skeletal muscle oxidative capacity, fiber type, and metabolites after lung transplantation.

Lung transplant (LTx) recipients have a low peak work rate, peak oxygen consumption (V O2peak), and early lactate threshold on incremental exercise. We hypothesized that LTx recipients have reduced oxidative function and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling and a resting quadriceps femoris punch muscle biopsy were performed. Muscle specimens were analyzed for fiber type proportion, metabolites, oxidative and glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR) using standard techniques. The results showed that mean V O2peak in LTx recipients was 52% of control subjects. Compared with the control subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower activity of the mitochondrial enzymes glutamate dehydrogenase (GDH), citrate synthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-dehydrogenase (HAD). There was no difference in the activities of anaerobic enzymes, except for higher phosphofructokinase activity; (3) a lower proportion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaerobic metabolism. The reduced type I fiber proportion and severely reduced mitochondrial oxidative capacity may play an important role in exercise limitation after LTx.

Adult↗

PubMed1999

Maximizing the utilization of donor organs offered for lung transplantation.

The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors and therapeutic manipulation where appropriate. This study aims to assess the impact of utilization of marginal donors and aggressive donor management. A comparison between published donor criteria and local practice is made, allowing assessment of the effect of using marginal donors on outcome. Donor management included antibiotic therapy, strict fluid management, physiotherapy, bronchoscopy and bronchial toilet, and alteration of ventilatory settings including initiation of pressure support. Blood gases were repeated to assess the results of interventions. Between January 1, 1995 and May 31, 1998, we performed 140 transplants from 112 of 219 (51%) lung donor offers. Of these donors, 48 (43%) satisfied all published criteria for suitable donor organs (Group 1 = ideal donors) and 64 (57%) did not (Group 2 = marginal donors). Criteria breached by the marginal donors were: an initial ratio of arterial oxygen pressure to fraction of inspired oxygen (PaO2/FIO2) < 300 mm Hg (n = 20), abnormal radiology (n = 39), pulmonary infection (n = 24), 20 pack-years smoking (n = 5) and age > 55 yr (n = 4). Therapeutic manipulation resulted in improvement in the PaO2/FIO2 ratio in 20 donors (Group 3) who would not otherwise have been used. Immediate and 24 h postoperative gas exchange and length of intensive care unit (ICU) stay was not different for recipients from donors from all three groups. Overall survival was 94% at 30 d, 83% at 1 yr, 70% at 2 yr, and 62% at 3 yr and was not significantly different from the three groups. We conclude that organ utilization can be maximized by therapeutic manipulation and utilization of marginal donors without compromising results from transplantation.

Adult↗

PubMed1999

In stable lung transplant recipients, exhaled nitric oxide levels positively correlate with airway neutrophilia and bronchial epithelial iNOS.

In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Variable degrees of airway inflammation are present in stable lung transplant recipients (LTR), and may lead to airway remodeling and chronic graft dysfunction. The hypothesis tested is that in stable LTR, eNO concentrations would reflect the expression of inducible (iNOS) (but not constitutive [cNOS] nitric oxide synthase) in the bronchial epithelium as well as the degree of airway inflammation. We determined eNO concentrations in 20 stable LTR, free of infection, rejection, or obliterative bronchiolitis (OB). At routine bronchoscopy, we measured the differential cell count on bronchoalveolar lavage (BAL) and a quantitative assessment of iNOS and cNOS expression in endobronchial biopsies by immunohistochemistry. Mean +/- SEM eNO concentrations in stable LTR were not significantly different from control subjects (13 +/- 0.7 ppb versus 14.2 +/- 0.49; p = 0.42). Percent BAL neutrophils was 11.5 +/- 3.2 which was significantly higher than in a group of local control subjects (1.7 +/- 0.6; p < 0.001). The bronchial epithelium and lamina propria contained abundant iNOS but cNOS was present only in the lamina propria. Using regression analysis, percent BAL neutrophils (r(2) = 0.82; p < 0.0001) and iNOS expression in the bronchial epithelium (r(2) = 0.75; p < 0.0001), but not in the lamina propria (r(2) = 0.16; p = 0.08), were positively predictive of eNO. There was an inverse relationship between cNOS and eNO. We conclude that eNO concentrations although normal for the group, still reflect the degree of airway inflammation in stable LTR. Epithelial iNOS appears to be the major source of eNO and expression of cNOS may be downregulated with increasing iNOS expression.

Biopsy↗

PubMed1999

Anaesthesia and postoperative pain management for bilateral lung volume reduction surgery.

Bilateral lung volume reduction surgery was introduced into Australia in 1995 for treatment of selected patients with emphysema. We present our experience of the anaesthetic management of our first 55 cases and describe factors associated with outcome. There were four postoperative deaths (7%). Mean (SD) total operation time was 231 (72) minutes. Median intensive care unit (ICU) stay was 26 hours. There was a significant improvement in postoperative lung function (FEV1, VC, 6-minute walk test, all P < 0.001). Eight patients (15%) required reintubation for respiratory failure; three of these patients subsequently died. With multivariate analysis, total operation time was the only significant predictor of length of ICU stay R2 = 0.25, P = 0.001), which itself was the only significant predictor of hospital stay duration (R2 = 0.36, P < 0.001).

Adult↗

PubMed1999

Coronary artery disease in potential lung transplant recipients > 50 years old: the role of coronary intervention.

STUDY OBJECTIVES: To review the experience of the Alfred Hospital in the systematic assessment of coronary artery disease (CAD) using coronary angiography (CA), and the subsequent management of CAD, in potential lung transplant recipients. DESIGN: Retrospective study. SETTING: The Alfred Hospital Lung and Heart Transplant Service. PATIENTS: CAD risk factors were sought in potential recipients of lung transplantation (LTx) who were > 50 years old, including a history of smoking, male gender, hypertension, diabetes, hypercholesterolemia, angina, and a family history of CAD. When feasible, and in the presence of more than one cardiac risk factor, CA was performed. RESULTS: From 243 referral patients who were > 50 years old, 97 were listed for LTx, and 77 underwent LTx. Four patients were refused LTx on the basis of CAD. Of 101 patients undergoing a detailed cardiac assessment for LTx, 83 had smoked, 56 were male, 48 had hypercholesterolemia, 22 had hypertension, 4 had diabetes, and 3 had a history consistent with angina. Eighty-five patients underwent CA. In 32 cases, CA revealed CAD, and half of these cases were significant stenoses. Eight patients who were assessed required intervention. Five patients of this group have been transplanted; of these, three patients underwent coronary artery grafting at the time of LTx, and two patients underwent preoperative angioplasty or stenting. Only one of these five patients died < 90 days postoperatively. CONCLUSION: Significant CAD is a common finding in older patients who are presenting for LTx. Coronary revascularization for severe large vessel stenoses can allow safe LTx. CAD risk factors may predict who should undergo CA, but further studies of clinical and noninvasive assessments of CAD are needed if CA is to be safely avoided in patients at low risk of CAD.

Combined Modality Therapy↗

PubMed1998

Endobronchial biopsy and bronchoalveolar lavage in stable lung transplant recipients and chronic rejection.

We have obtained endobronchial biopsies (EBB), bronchoalveolar lavage (BAL), and transbronchial biopsies (TBB) in 17 stable lung transplant recipients (sLTR), 8 subjects with physiologic evidence of chronic rejection (BOS), and 9 normal subjects. A striking finding was the marked neutrophilia in BAL samples from patients with BOS, in the carefully screened absence of infection. A statistically higher neutrophil count was also present in the sLTR group relative to the normal group. Median BAL neutrophil count in BOS was 100 x 10(3)/ml, range 13-1,661 10(3)/ml (p < 0.001 relative to normal subjects and sLTR). Median BAL neutrophil count in sLTR was 7 x 10(3)/ml, range 1-81 10(3)/ml (p < 0.01 relative to normal subjects). Normal subjects had a median BAL neutrophil count of 3 x 10(3)/ml, range 1-7 10(3)/ml. There was evidence of a predominance of CD8 lymphocytes in BAL from sLTR and BOS with a lower CD4/CD8 ratio in both compared to normal subjects (p < 0.05). EBB mononuclear cell counts, class II major histocompatibility complex expression, and T-cell activation markers were normal in BOS, in contrast to the sLTR group. Our data may be consistent with BOS, representing a relative resolution of an active mononuclear cell chronic inflammation, perhaps at the expense of airway fibrosis. The relevance of the BAL neutrophilia and its role in BOS pathogenesis need further longitudinal investigation.

Adult↗

PubMed1998

Central sleep apnoea in congestive heart failure despite vagal denervation after bilateral lung transplantation.

Nonhypercapnic central sleep apnoea is a disorder of respiratory control characterized by hyperventilation previously attributed to the stimulation of either pulmonary vagal afferent nerve fibres or respiratory chemoreceptors. This report describes central sleep apnoea in a patient with congestive heart failure following bilateral lung transplant in whom pulmonary vagal afferent nerve activity was absent.

Heart Failure↗

PubMed1998

Body mass index as a predictor of survival in adults with cystic fibrosis referred for lung transplantation.

BACKGROUND: The timing of referral and listing for lung transplantation in adults with cystic fibrosis is influenced by many factors including pulmonary function, body mass index (BMI), sex, and patient and physician choice. This study aimed to analyze the effect of these variables on waiting list and postoperative mortality rates. In particular, low BMI is suggested to portend a poor outcome after transplantation. METHODS: All patients with cystic fibrosis referred to our institution (n = 92) between 1989 and 1996 were reviewed, and the effect on survival of BMI, sex, and other covariates was analyzed by use of Cox proportional hazards regression. RESULTS: Forty-five transplantations were undertaken with a mean waiting time of 226 days (range 1 to 678). Fifteen of the 62 listed patients died before transplantation with a mean time to death of 160 days (range 8 to 533). Fifteen patients died after transplantation. BMI at the time of listing predicted waiting list mortality (P < .05). Female sex tended to increase waiting list mortality rates, such that the combination of BMI less than 18 kg/m2, and female sex was associated with a 21% 1-year waiting list survival without transplantation. Age, forced expiratory volume in 1 second, sex, BMI, and date of transplantation did not predict postoperative survival. CONCLUSION: Patients with cystic fibrosis (particularly women) referred for lung transplantation with a BMI less than 18 kg/m2 are at high risk of death over the next 12 months. With this in mind, they should not be denied transplantation unduly while attempts are made to increase weight, especially because pretransplantation BMI does not influence posttransplantation survival.

Adult↗

PubMed1997

Lung volume reduction surgery for emphysema.

OBJECTIVE: To report the results of lung volume reduction surgery (LVRS) for severe emphysema in Australia. SETTING: A tertiary teaching hospital. DESIGN: A prospective study of a consecutive case series. PARTICIPANTS: 20 patients (mean age, 56 years) with severe emphysema--mean forced expiratory volume in one second (FEV1), 0.72 L (28% of predicted) and severe gas trapping (mean residual volume, 286% of predicted). INTERVENTION: Bilateral apical LVRS was performed via a median sternotomy with a linear stapler; bovine pericardial strips were used to reinforce the staple line. RESULTS: There was a 95% survival, and a mean (range) inpatient stay of 17 (8-45) days. No complications occurred in nine patients; a further six patients had only minor complications. Five patients had major complications (sputum retention requiring reintubation, persistent air leak requiring reoperation, duodenal perforation, and epidural haemorrhage); one patient died from multiorgan failure at 28 days. Intercostal drainage was left in situ for a mean of eight days. The results of FEV1, Medical Research Council (MRC) Dyspnoea Score and six-minute walk test improved in more than 90% of patients. FEV1 improved an average of 0.35 L (54% over baseline) (P < 0.001). Mean MRC Dyspnoea Score decreased from 3.4 to 2.1 (P < 0.001). Mean distance for the six-minute walk test increased from 306 to 431 metres (P < 0.001). CONCLUSION: Our experience confirms that LVRS produces worthwhile early outcomes for a subgroup of patients with severe emphysema. The clinical, economic and ethical questions raised by this new therapy will need to be assessed.

Adult↗

PubMed1997

Early and long-term functional outcomes in unilateral, bilateral, and living-related transplant recipients.

Lung transplantation offers the possibility of improved quality of life and survival in patients with severe pulmonary and pulmonary vascular disease. Since the first human lung allotransplantation in 1963, survival has moved from hours or days into the present era of long-term (years) survival in many recipients. Measurement of outcome has now extended to measurement of exercise capacity and quality of life. A substantial improvement in quality of life is seen; however, exercise capacity remains moderately impaired in spite of the return (in many) of near normal cardiopulmonary function, suggesting peripheral limitation to exercise. Recently, fiber type changes and abnormal oxidative metabolism have been shown in the skeletal muscle of stable lung transplant recipients. This suggests a persistence of a pretransplant skeletal muscle injury and/ or the effects of post-transplant immunosuppression (particularly Cyclosporin A and corticosteroids).

Exercise Test↗

PubMed1997

Immunopathological changes in the airways of stable lung transplant recipients.

BACKGROUND: Pathological obliterative bronchiolitis, characterised by inflammation and occlusion of airways, is a serious complication of lung transplantation. Endobronchial biopsy (EBB) provides a means of examining transplanted airways. This study aimed to investigate the role of EBB samples in revealing early signals of airway injury. METHODS: In 18 stable lung transplant recipients with close to maximal lung function (median FEV1, best after transplantation 100%, interquartile range 98-100%) EBB samples were taken simultaneously with transbronchial biopsy samples and bronchoalveolar lavage (BAL) fluid (median 195 days after transplantation). OCT embedded specimens were snap frozen on an isopentane slurry made with liquid nitrogen and 7 microns sections were stained with monoclonal antibodies using a three stage immunoperoxidase method. RESULTS: Compared with nine non-transplanted control subjects, EBB specimens from the stable transplant group had significantly increased CD8 positivity (median 53 versus 27 cells/mm basement membrane, p = 0.04; 95% CI for the difference 1 to 46)) and increased HLA-DR positivity (median 84 versus 26 cells/mm basement membrane, 95% CI for the difference 6 to 115). There was an increase in CD68 positive cells in the EBB specimens from transplant recipients of borderline significance (median 92 versus 68, p = 0.08, 95% CI for the difference 1 to 84). CD3, CD4, and CD25 counts were similar in the two groups. EBB findings were not influenced by age, sex, indication for transplant, immunosuppression doses or levels, nor the presence of airway commensals in the BAL fluid. CONCLUSIONS: EBB is practicable in a transplant setting and provides information about bronchial inflammatory changes. It is likely that there is ongoing inflammation, possibly rejection mediated, even in healthy lung transplant recipients despite triple immunosuppression.

Adult↗

PubMed1997

Bronchial hyperresponsiveness in lung transplant recipients: lack of correlation with airway inflammation.

BACKGROUND: Bronchial hyperresponsiveness (BHR) to methacholine has been reported to occur in most lung transplant recipients. BHR to physical stimuli such as exercise and non-isotonic aerosols has not been as extensively studied in this subject population. This report aims to assess the presence and degree of BHR to methacholine and hypertonic saline in stable lung transplant recipients and to relate it to the presence of airway inflammation. METHODS: Ten patients undergoing bilateral sequential lung transplantation and six heart-lung transplant recipients, all with stable lung function, were recruited 66-1167 days following transplantation. Subjects underwent a methacholine challenge and bronchoscopy for sampling of bronchoalveolar lavage fluid, transbronchial and endobronchial biopsy tissues. Hypertonic saline challenge was performed six days later. RESULTS: Nine of the 16 transplant recipients had positive methacholine challenges (geometric mean PD20 0.18 mg, interquartile range 0.058-0.509) and three of these subjects also had positive hypertonic saline challenges (PD15 = 2.3, 33.0, and 51.5 ml). No clear relationship was found between BHR to either methacholine or hypertonic saline and levels of mast cells, eosinophils or lymphocytes in samples of biopsy tissue or lavage fluid. CONCLUSIONS: Most of the lung transplant recipients studied were responsive to methacholine and unresponsive to hypertonic saline. BHR was not clearly related to airway inflammation, suggesting an alternative mechanism for BHR following lung transplantation from that usually assumed in asthma.

Adult↗