Pulmonary Type B Niemann-Pick Disease Successfully Treated with Lung Transplantation.

BACKGROUND: Niemann-Pick Disease (NPD) type B is a rare autosomal recessive disease characterised by hepatosplenomegaly and pulmonary disease, highlighted by preserved volumes and diminished diffusion capacity of the lung for carbon monoxide (DLCO) on pulmonary function tests (PFTs). There is no current accepted treatment for the disease. We present a case of a successful bilateral lung transplant in a patient with a DLCO of 14%, and significant pulmonary changes attributable to NPD type B on computed tomography (CT) chest, and both microscopic and macroscopic assessment of the lung explant. To the author's knowledge this is only the third case of lung transplantation in a patient with NPD type B and is one of two current living patients post lung transplantation for NPD type B. CASE REPORT: A 64-year-old male patient underwent bilateral lung transplantation for NPD type B. Preoperative PFTs demonstrated preserved volumes with significantly decreased DLCO, with imaging showing a diffuse reticular interstitial pattern, typical of chronic fibrotic lung disease. The patient suffered from primary graft dysfunction type 3 in the postoperative period as well as rejection managed with methylprednisolone and intravenous immunoglobulin. The patient improved steadily and was discharged 80 days post-transplantation. CONCLUSIONS: This case is only the third reported case of lung transplantation in a patient with NPD type B and the second case of a patient with NPD type B currently living post-transplantation, being at postoperative day (POD) 267 at the time of manuscript drafting. It demonstrates that lung transplantation, although hazardous, is a viable strategy for treatment in patients with NPD type B who have significant pulmonary involvement.

Interventional bronchoscopy for the management of airway complications following lung transplantation.

STUDY OBJECTIVES: To assess the efficacy and complications of different interventional bronchoscopic techniques used to treat airway complications after lung transplantation. DESIGN: Retrospective study. SETTING: Heart-lung transplant unit of a university hospital. PATIENTS: From November 1986 to January 2000, interventional bronchoscopy was performed in 41 of 312 lung transplant recipients (13.1%) for tracheobronchial stenosis, bronchomalacia, granuloma formation, and dehiscence. INTERVENTIONS: Dilatation, stent placement, laser or forceps excision. MEASUREMENTS AND RESULTS: Mean (+/- SE) improvement in FEV(1) in 26 patients undergoing dilatation for a stenotic or a combined lesion was 93 +/- 334 mL or 8 +/- 21%. In seven of these patients not proceeding to stent placement, mean improvement in FEV(1) was 361 +/- 179 mL or 21 +/- 9%. Patients needing stent placement after dilatation had a mean change in FEV(1) after dilatation of - 5 +/- 325 mL or 3 +/- 23%, and an improvement of 625 +/- 480 mL or 52 +/- 43% after stent insertion. Mean improvement in FEV(1) for patients treated with stent insertion for bronchomalacia was 673 +/- 30 mL or 81 +/- 24%. Complications of airway stents were migration (27%), mucous plugging (27%), granuloma formation (36%), stent fracture (3%), and formation of a false passage (6%). Mortality associated with interventional bronchoscopy was 2.4% (1 of 41 patients). For patients with airway complications successfully undergoing interventional bronchoscopy, the overall 1-year, 3-year, and 5-year survival rates were 79%, 45%, and 32%, respectively, vs 87%, 69%, and 56% for those without airway complications (p < 0.05). CONCLUSION: Only a small number of patients with airway stenosis after lung transplantation will respond to bronchial dilatation alone. Patients with airway complications after lung transplantation have a higher mortality than patients without airway complications.

Lung transplantation: management and complications.

Lung transplantation has become an accepted treatment modality for end stage lung disease including emphysema, fibrosing alveolitis, cystic fibrosis, pulmonary hypertension and bronchiectasis. Despite the use of potent immunosuppressive drugs, acute rejection occurs frequently, especially in the first few weeks and months after transplantation. Bacterial, viral and fungal infections frequently occur in lung transplant recipients. Rapid diagnosis and adequate treatment of infections is needed. The side effects with the use of long term immunosuppressive agents includes renal toxicity, hypertension, neurotoxicity, hyperlipidemia, leucopoenia, hyperglycaemia, weight gain, osteoporosis and malignancy. However, obliterative bronchiolitis (OB) which is regarded as a chronic rejection process remains the dominant cause of morbidity and mortality in the long-term survivors of lung transplantation. This article focuses on the postoperative and long term management of lung transplant recipients.

Lung transplantation for chronic obstructive pulmonary disease at St Vincent's Hospital.

BACKGROUND: Lung transplantation (LTx) offers selected patients with end-stage chronic obstructive pulmonary disease (COPD) an improved quality of life and possibly enhanced survival. AIM: To determine local outcomes of LTx for COPD we analysed 173 consecutive heart-LTx (n = 8), single LTx (SLTx; n = 99) and bilateral LTx (BLTx; n = 66) carried out at a single institution during 1989-2003 for smoking-related emphysema (E) (n = 112) and emphysema related to alpha-1 antitrypsin deficiency (AATD) (n = 61). METHODS: There were 98 men and 75 women with a mean age of 50 +/- 6 years (standard deviation) (range 32-63 years). Median waiting time was 113 days (interquartile range (IQR) 50-230 days), and median inpatient stay was 13 days (IQR 9-21 days). RESULTS: Perioperative survival (30 days) was 95% with deaths from sepsis (n = 5), cerebrovascular accident (n = 3) and multiorgan failure (n = 1). Mean follow-up period was 1693 +/- 1302 days (2-4,805 days). The 1-, 5- and 10-year survivals (%) were similar for patients with E and AATD (P = 0.480 log rank) at 86 +/- 5, 57 +/- 7 and 31 +/- 11, respectively, but 1- and 5-year survivals for E were higher after BLTx than after SLTx (97 +/- 2 and 81 +/- 8 vs 85 +/- 4 and 47 +/- 6) (P = 0.015). Pretransplant body mass index, forced expiratory volume in 1 second, forced vital capacity, PaCO(2), PaO(2), six-minute walk distance, home oxygen use, age, sex, cytomegalovirus donor-recipient mismatch, cardiopulmonary bypass use, year of transplant and ischaemic time did not influence survival after LTx. Increasing donor age was a survival risk factor for patients with E but not for those with AATD (hazard ratio 1.043; 95%confidence interval 1.014-1.025). CONCLUSION: Survival after LTx for COPD is similar to survival for other forms of solid organ transplantation, in part reflecting risk factor management.

The spectrum of mycobacterial infection after lung transplantation.

Despite the success of lung transplantation, infection is one of the leading causes of morbidity and mortality. Mycobacterial infections have been reported rarely, with the majority due to Mycobacterium tuberculosis. Our aim was to assess the incidence, etiology, and clinical outcome of mycobacterial infection after lung transplantation; to do so, we have studied retrospectively all lung and heart- lung transplants performed over a 12-yr period between November 1986 and June 1998 (n = 261). Twenty-three patients (9%) (M:F, 11:12) were diagnosed with mycobacterial infections in 25 sites, including n = 19, pulmonary (M. avium complex [n = 13], M. tuberculosis [n = 2], M. abscessus [n = 2], M. asiaticum [n = 1], and M. kansasii [n = 1]) and n = 6 extrapulmonary (M. haemophilum [n = 5] and M. abscessus [n = 1]) infections. Time to diagnosis from transplantation was 677 +/- 735 d (range, 2- 3,086 d). Three episodes of transient colonization with M. avium were not treated; the remaining (22 of 25, 88%) were treated. Initial baseline therapy for nontuberculous mycobacteria included clarithromycin, rifampicin, ciprofloxacin, and/or ethambutol. All cutaneous lesions resolved completely, while clinical and graft function improved in 11 of 16 (69%) and 8 of 16 (50%) of patients treated, respectively. Seventeen of 23 patients (72%) survived at a follow-up of 1,658 +/- 759 d (range, 522-3,285 d). Complications, predominantly due to rifampicin, included gastrointestinal intolerance and an increased tendency for rejection. There were no deaths attributable to mycobacterial disease or therapy. We conclude that mycobacterial infection, particularly due to nontuberculous mycobacteria, is relatively common after lung transplantation and may be an unrecognized cause of graft dysfunction. Early treatment of cutaneous lesions is associated with excellent control; however, graft dysfunction may be permanent. Although drug toxicity and interactions with immunosuppressive agents were not infrequent, the majority of these infections can be managed successfully.

Bronchoscopic dilatation in the management of benign (non-transplant) tracheobronchial stenosis.

BACKGROUND: Tracheobronchial stenosis in the adult patient is a recognized postoperative complication of sleeve resection or lung transplantation, but also occurs in medical conditions such as sarcoidosis, tuberculosis, postintubation/tracheostomy or post-radiation. AIMS: To assess the response of bronchoscopic dilatation in the management of benign (non-transplant) tracheobronchial stenosis and the longevity of symptomatic relief. METHODS: Eight patients underwent bronchoscopic dilatation for benign (non-transplant) tracheobronchial stenosis. The indications were post-tuberculous bronchostenosis (n = 3), post-tracheostomy/endotracheal intubation strictures (n = 3), postradiation bronchostenosis (n = 1) and narrowing of the tracheal lumen following a muscle flap surgery for tracheoesophageal fistula (n = 1). RESULTS: Dilatation alone was effective in the management of four patients (50%). Two patients had stent placement postdilatation, one patient had tracheal resection and primary anastomosis and one patient had laser ablation for restenosis followed by balloon dilatation. All patients had clinical improvement. One patient was successfully weaned off mechanical ventilation and extubated. There was no procedure-related mortality and all patients were alive and well at the time of reporting, with a mean duration since procedure of 123 +/- 105 (range 8-340) weeks. The complications observed were granuloma formation at the site of laser excision and restenosis, each in one patient. CONCLUSIONS: Bronchoscopic dilatation is a safe and effective modality in the initial assessment and management of benign tracheobronchial stenosis. Stent placement and Nd:YAG laser therapy complement a dilatation procedure in the combined bronchoscopic treatment of benign tracheobronchial stenosis.

Opportunistic lung infection with Corynebacterium pseudodiphtheriticum after lung and heart transplantation.

Corynebacterium pseudodiphtheriticum is usually regarded as a harmless commensal of the skin and mucous membranes. We describe two cases of bronchiolitis and bronchitis after lung and heart transplantation, respectively, in which this organism was strongly implicated as the pathogen.

Diagnostic value of follow-up transbronchial lung biopsy after lung rejection.

Although transbronchial lung biopsy (TBBx) is widely acknowledged as the "gold standard" for diagnosis of acute rejection, controversy exists regarding the need to perform follow-up procedures. Over a 5-yr period, we performed 1,142 TBBx of which 173 were follow-up TBBx in 99 patients with pulmonary allograft rejection greater than or equal to International Society for Heart and Lung Transplantation (ISHLT) grade A(2) on initial TBBx. Rejection on the previous 173 TBBx was associated with lymphocytic bronchiolitis/bronchitis (LBB) > or = ISHLT grade B(2) in 82 patients and with cytomegalovirus (CMV) pneumonitis in 16 patients. Persistent rejection (> or = A(2)) was observed in 45 of 173 (26%) follow-up TBBx. Persistent B grade rejection (> or = B(2)) was present in 28 patients whereas new B grade rejection developed in 11 patients with > or = A(2) grade rejection. Rejection > or = B(2) was significantly (p < 0.05) associated with rejection > or = A(2). Fifteen follow-up TBBx showed new B grade rejection without signs of > or = A(2) rejection. A new diagnosis of CMV pneumonitis was made in 33 of 173 (19%). CMV pneumonitis occurred in 35 follow-up TBBx, four associated with > or = A(2) rejection and eight with > or = B(2) rejection. The overall incidence of bronchiolitis obliterans syndrome (BOS) in both groups was similar. Patients with persistent rejection on follow-up TBBx developed BOS at a median of 1.3 yr and median of 2.0 yr (p = not significant [NS]) posttransplantation. The practice of follow-up TBBx after rejection within 2 yr posttransplant is clinically useful as it provides valuable diagnostic information.

Achilles tendon disease in lung transplant recipients: association with ciprofloxacin.

Achilles tendonitis or rupture are uncommon complications following the use of fluoroquinolones, with a reported incidence in the general population of 0.4%. The aims of the current study were to determine the incidence of Achilles tendon disease (ATD) in lung transplant recipients (LTR) and to identify risk factors. Questionnaires were sent to 150 LTR of whom 101 responded (67%). Twenty-two LTR (21.8%) experienced ATD (tendonitis 16, rupture six). The mean age of LTR who developed ATD was 52.9+/-6.1 yrs (range: 19-63.5 yrs). Only the use of ciprofloxacin was significantly associated with ATD (p<0.05). Age, sex, underlying disease necessitating transplantation, serum creatinine and cyclosporine levels were not associated with ATD. The association between ciprofloxacin and ATD was not dose related. Of the 72 LTR who had received ciprofloxacin, 20 (28%) developed ATD (tendonitis 15, rupture five). In patients receiving ciprofloxacin, there was no association between the mean cumulative dose of prednisolone and ATD. Tendon rupture occurred with a lower ciprofloxacin dosage than tendonitis and the mean recovery duration was significantly longer. To conclude, lung transplant recipients receiving ciprofloxacin are at significant risk of developing Achilles tendon disease. The association between ciprofloxacin and Achilles tendon disease appears to be idiosyncratic rather than dose-related.

Prophylactic nasopharyngeal tube insertion prevents acute hypoxaemia due to upper-airway obstruction during flexible bronchoscopy.

Insertion of a nasopharyngeal tube (NT) is a highly effective approach to the management of acute hypoxaemia during flexible bronchoscopy (FB) in lung -transplant recipients. We noted that lung transplant recipients undergoing FB who had been treated previously with NT insertion had further episodes of oxygen desaturation (<90%), despite supplemental oxygen therapy. Prophylactic NT insertion prevented acute hypoxaemia in the majority of lung transplant recipients, with previously documented FB-related oxygen desaturation secondary to UAO. Additional jaw support may be needed in some patients with severe upper-airway obstruction.

Maintenance therapy with oral ganciclovir after treatment of cytomegalovirus infection.

While oral ganciclovir (OGCV) has been used as primary prophylaxis in patients at high risk for cytomegalovirus (CMV) infection after solid organ transplantation, its value in secondary prophylaxis is unknown. We have examined the use of OGCV as maintenance therapy following confirmed CMV infection on 16 occasions in 15 patients, in kidney (n = 4), kidney-pancreas (n = 3) lung (n = 6) and heart-lung (n = 1) recipients. OGCV was used in two distinct clinical situations. One group (n = 7) received OGCV as consolidation therapy (mean duration of 21 +/- 5 d) following i.v. ganciclovir induction therapy (mean duration of 16 +/- 5 d) for acute CMV infection, and sustained remission was achieved in 6/7 patients for a median follow-up of 300 d. In the second scenario, OGCV suppressed clinical disease in all patients with relapsing CMV infection (n = 9), with minimal or absent toxicity with a median follow-up of 152 d. OGCV reduced morbidity by allowing removal of central lines used for long-term i.v. therapy in patients with poor peripheral access. Hence, this study demonstrates the safe and effective use of OGCV as consolidation therapy after standard induction treatment with i.v. ganciclovir, and as long-term suppressive therapy in transplant recipients with recurrent CMV infection.