Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.

High proportion of rare and compound epidermal growth factor receptor mutations in an Australian population of non-squamous non-small-cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation positivity in primary non-small-cell lung cancer (NSCLC) may confer increased sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy with improved progression-free survival over EGFR wild-type tumours. Some mutation subtypes may not confer such TKI sensitivity. The incidence of rare and compound subtypes in the Australian lung cancer population is not fully defined. AIMS: The aim of the study was to audit the incidence of EGFR mutation in serial cases of primary non-squamous NSCLC presenting to two multidisciplinary team meetings in metropolitan Sydney for incidence, type of mutation and phenotypic association with mutation positivity. METHODS: Serially presenting cases of primary non-squamous NSCLC were tested for EGFR mutation. The cases presented to either of two multidisciplinary team meetings in metropolitan Sydney and were referred for EGFR mutation testing on the basis of non-squamous NSCLC histopathology. Samples from the two sites were analysed for EGFR mutation at one of three different laboratories, each using a slightly different assay. Data on phenotypic characteristics, smoking history and clinicopathological features of the tumour were collected. RESULTS: There is a relatively high incidence of EGFR mutation in non-squamous NSCLC in a series of patients drawn from two metropolitan multidisciplinary team meetings in Sydney at a rate of 23.8%. A high proportion of rare and compound EGFR mutations were identified (6/32 mutation positive cases, 18.8%). CONCLUSIONS: The incidence of EGFR mutation may be higher in Australian populations than in other populations of predominantly European origin. Rare and compound EGFR mutations may occur and may have implications for treatment that differ from classically activating mutations.

Myositis due to the microsporidian Anncaliia (Brachiola) algerae in a lung transplant recipient.

Microsporidia are obligate intracellular parasites, more closely related to fungi than protozoa on molecular phylogenetic analysis, and are known to be a rare cause of opportunistic infection in immune compromised patients including human immunodeficiency virus-positive patients and solid organ transplant recipients. We report the first case to our knowledge of microsporidial myositis in a lung transplant recipient. He was 49 years old and had received a lung transplant in 2000 for cystic fibrosis. He presented in 2009 with fevers, chronic diarrhea, myalgia, and pancytopenia, and developed progressive weakness and neurological symptoms before his death 35 days after hospital admission. Multiple investigations, including stool culture, rectal biopsy, colonoscopy, cerebrospinal fluid examination, bone marrow biopsy, lung biopsy, and bronchoalveolar lavage, failed to reveal a definite cause for the patient's deterioration. The diagnosis of microsporidial infection was made on post-mortem light microscopic examination of tissue sections of the tongue and deltoid muscle. Light microscopy diagnosed a microsporidial myositis, confirmed by transmission electron microscopy, which suggested that the organism was Brachiola species. The identity of the organism was confirmed by polymerase chain reaction as Brachiola algerae (recently renamed Anncaliia algerae). The case highlights the need to consider protozoal organisms in the differential diagnosis of myalgia and multisystemic infections in immune compromised patients.

Diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration compared with transbronchial and endobronchial biopsy for suspected sarcoidosis.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate and minimally invasive technique that has been shown to have excellent diagnostic yield in the investigation of mediastinal and hilar lymphadenopathy. There is, however, little evidence comparing this procedure to the traditional diagnostic approach of transbronchial lung (TBLB) and endobronchial (EB) biopsies combined with characteristic clinical and radiological features in sarcoidosis. AIM: To compare the diagnostic yield of EBUS-TBNA, TBLB and EB in patients with suspected sarcoidosis. METHODS: Data from 40 consecutive patients with suspected sarcoidosis who underwent combined EBUS-TBNA with TBLB and EB biopsies were recorded. RESULTS: A total of 37 patients was confirmed as sarcoidosis, and three had other diagnoses. There was no difference in diagnostic accuracy rates between EBUS-TBNA and TBLB for all stages of sarcoidosis (84% vs 78%, P= 0.77). Combined EBUS-TBNA and TBLB procedures yielded a diagnostic accuracy of 100%. There was a highly significant difference in diagnostic accuracy between EBUS-TBNA and EB in stage I (80% vs 27%) (P < 0.01) and stage II disease (86% vs 27%) (P < 0.01). Similarly, a highly significant difference in diagnostic accuracy was seen between TBLB and EB (P < 0.01). No adverse events occurred. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspiration alone has a high diagnostic yield with a very low complication rate for patients with suspected sarcoidosis.

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.

Guideline for the management of chronic obstructive pulmonary disease (COPD): 2004 revision.

OBJECTIVE: To revise the South African Guideline for the Management of Chronic Obstructive Pulmonary Disease (COPD) in the light of new insights into the disease and the value of new treatment approaches and drugs. New aspects considered include: A growing awareness of the impact of COPD in South Africa, and the urgent need for prevention strategies. The role of concurrent exposures to domestic and occupational atmospheric pollution, and previous lung infections including tuberculosis. The need to consider as goals of treatment both prevention of exacerbations and improvement of quality of life (health status) of patients with COPD. The development of both long-acting beta2-agonist and anticholinergic drugs for use in COPD. Emerging evidence on a limited role for inhaled corticosteroids in the treatment of COPD. RECOMMENDATIONS: These include primary and secondary prevention; early diagnosis; staging of severity; assessment of reversibility with bronchodilator and, in some, responsiveness to corticosteroids; use of bronchodilators and other forms of treatment; rehabilitation; and treatment of complications. Advice is provided on the management of acute exacerbations, and the approach to air travel, prescribing long-term oxygen, and lung surgery including lung volume reduction surgery. Prevention, both primary and secondary, remains the most cost-effective measure in the management of COPD, and deserves more emphasis, particularly on the part of health care professionals. Primary prevention involves reducing public exposure to cigarette and other forms of smoke, and reduction of atmospheric pollution, and secondary prevention limits exposure and resultant progression in those with established disease. Spirometry is essential for the diagnosis of COPD and in staging severity. In addition, a new classification of severity that considers other indices of functional impairment is provided. Treatment involves a progression from 'as-needed' bronchodilators, through the addition of other more effective bronchodilators, usually in combination, in more severe stages. The importance of assessing potential reversibility in every patient with persistent symptoms, and of the limited role of oral and inhaled corticosteroids (ICS), is emphasised. These approaches also reduce exacerbations and may result in cost savings and improved prognosis. A practical low-cost approach to rehabilitation is proposed. OPTIONS: Treatment recommendations are based on the following: the recommendations of the Global Obstructive Lung Disease (GOLD) initiative, which provides an evidence-based comprehensive and up-to-date review of treatment options; independent evaluation of the level of evidence in support of some of the new treatment trends; and consideration of factors that influence COPD management in South Africa, including lung co-morbidity and drug availability and cost. OUTCOMES: The use of bronchodilators is driven by the presence of symptoms, but regular assessment of benefit, based on objective criteria, is essential. Several forms of treatment reduce exacerbations, the most effective of these is smoking cessation. EVIDENCE: Working group of clinicians and clinical researchers following detailed literature review, particularly of studies performed in South Africa, and the GOLD guidelines. BENEFITS, HARMS AND COSTS: The guideline pays particular attention to cost-effectiveness in South Africa, and promotes the initial use of less costly options. It rejects empirical use of corticosteroids both oral and inhaled, and promotes smoking cessation, and selection of treatment based on objective evidence of benefit. It also rejects a nihilistic or punitive approach, even in those who are unable to break the smoking addiction. VALIDATION: The COPD Working Group comprised experienced pulmonologists representing all university departments in South Africa and some from private practice. All contributed to the development of the previous version of the South African guideline, and attend international meetings. One (JRJ) represents South Africa on the GOLD Guideline Executive. GUIDELINE SPONSOR: The meeting of the Working Group of the South African Thoracic Society was sponsored by an unrestricted educational grant from Boehringer Ingelheim (South Africa) (Pty) Ltd.

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.

Bilateral vocal cord palsy following interscalene brachial plexus nerve block.

Acute respiratory complications of an interscalene brachial plexus block include ipsilateral phrenic nerve and recurrent laryngeal nerve palsies. A 71-year-old woman who had undergone a total thyroidectomy for papillary carcinoma 35 years ago was administered a right interscalene brachial plexus block for a shoulder hemi-arthroplasty. Subsequently she developed acute respiratory distress associated with marked stridor secondary to an acute right vocal cord palsy, which was superimposed on what was assumed to be a preexisting left-sided vocal cord palsy. On extubation the patient was noted to develop stridor again necessitating reintubation and tracheostomy was performed two weeks later. The vocal cord palsies failed to resolve over the subsequent 18-month follow-up. We describe this case to highlight the significant risk of this procedure in patients with preexisting or suspected contralateral vocal cord palsy.

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.

Asthma management and perceptions in rural South Africa.

BACKGROUND: Many First World countries have endeavored to measure the impact of asthma on individuals with asthma and, in addition to this quality of life evaluation, have attempted to define the quality of care for this common chronic illness. OBJECTIVE: The primary objective of this research probe was to assist the National Asthma Program in South Africa with the formulation and delivery of its outreach program to rural asthmatic patients. METHODS: A discussion/questionnaire document was compiled by Partners in Research from established literature. All interviews were conducted in either the clinics, hospitals, or respondents' homes. Both adult asthmatic patients and parents of pediatric asthmatic patients were interviewed. Interviewing took place at seven rural health clinics across South Africa. Each interview included extensive demographic details, questions on asthma definition, symptoms and symptom triggers, family history, age at diagnosis, frequency of symptoms, and treatment. RESULTS: Thirty-five adult asthmatic patients and 27 parents of pediatric asthmatic patients were interviewed. Of the adults, 40% reported wheezing at least once a week (despite diagnosis and treatment) and 19% of children reported similar symptom exacerbations. Fifty-one percent of adults and 56% of children were awakened at least once a week by cough or wheeze. Quality of life measurement reflected that, on average, 37% of responders were frightened during an acute asthma attack, and 68% of parents reported fearing the death of their asthmatic children. Fifty-one percent of adults and 33% of children had been hospitalized at least once for asthma. Although respondents claimed regular training in use of inhaler device, only 43% of adults completed each step correctly. CONCLUSIONS: There is a great deal of fear and ignorance surrounding asthma and, therefore, there is a real need for a greater level of patient education even in the rural areas of South Africa. In rural South Africa, attention should be paid to nurses, because they play a greater role than doctors in management and education of asthma.

Guideline for the management of chronic asthma in adults--2000 update. South African Pulmonology Society Adult Asthma Working Group.

OBJECTIVE: To make recommendations for the cost-effective management of asthma incorporating recent advances in the understanding and treatment of asthma since the last guideline statement in 1992. The guideline is applicable to adults and children over 12 years of age. OPTIONS: Asthma should be graded according to standard severity criteria. The principle of 'hit early, hit hard' with corticosteroids to achieve rapid control is encouraged; thereafter treatment should be tailed down to the lowest dose of corticosteroids that maintains the aims of asthma treatment. OUTCOMES: The aims of asthma management should be achieved; these include: (i) avoidance of causative and trigger factors; (ii) abolition of symptoms and ability to lead a normal lifestyle; (iii) restoration of normal (or best possible) lung function; (iv) reduction of the risk of severe attacks; and (v) optimisation of treatment with minimal side-effects. EVIDENCE: Based on a selective review of randomised, controlled studies to support an evidence-based approach to treatment. BENEFITS, HARMS AND COSTS: Appropriate management of asthma should lead to a reduction in morbidity and mortality of asthma and a consequent reduction in cost of asthma care. Side-effects of corticosteroids are placed in perspective together with a strategy to minimise these effects. RECOMMENDATIONS: Asthma should be managed with inhaled corticosteroids as the most important anti-inflammatory treatment, except in the case of mild intermittent asthma which may be treated with beta 2 agonists on a pro re nata (prn) basis. It is preferable to add long-acting beta 2 agonists to low-dose inhaled corticosteroids before increasing corticosteroids. Leukotriene receptor antagonists are currently recommended for use in combination with inhaled corticosteroids pending further data on their long-term benefits. Differentiation of asthma from chronic obstructive pulmonary disease (COPD) is important. Early referral to a pulmonologist in difficult cases is encouraged. VALIDATION: Endorsed by the South African Pulmonology Society, the Allergy Society of South Africa and the South African Medical Association. The guideline is compatible with those of other international societies.

Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis.

Patients who have completed a treatment for severe pulmonary tuberculosis (TB) are often left with severe respiratory disability. There have been few prospective studies assessing the effect of treatment on lung function in such patients. The influence of antimicrobial chemotherapy on lung function was investigated over a six month period in patients with newly diagnosed pulmonary TB to test the hypothesis that treatment improves lung function, as well as to identify factors that may influence lung function outcome. Seventy-six patients were recruited into the study, of whom 74 completed the treatment programme. Forty-two were current smokers and 13 seropositive for the human immunodeficiency virus. Improvement in lung function occurred in 54% of patients, but residual airflow limitation or a restrictive pattern was evident in 28% and 24% of patients, respectively. The extent of lung infiltration (radiographic score) both at the outset and after chemotherapy was significantly and negatively related to forced expiratory volume in one second (FEV1) (% pred) (r=-0.41, and r=-0.46, respectively). The post-treatment serum C-reactive protein and alpha1-protease inhibitor levels were negatively associated with FEV1 (% pred) (r=-0.30 and r=-0.35, respectively). These findings demonstrate that, while antimicrobial chemotherapy may lead to improved lung function in patients with pulmonary tuberculosis, a large proportion of patients has residual impairment. The most significant factor influencing post-treatment lung function status, as measured by forced expiratory volume in one second (% predicted), is the pretreatment and post-treatment radiographic score, which acts as a marker of the extent of pulmonary parenchymal involvement in tuberculosis.

Influence of antimicrobial chemotherapy and smoking status on the plasma concentrations of vitamin C, vitamin E, beta-carotene, acute phase reactants, iron and lipid peroxides in patients with pulmonary tuberculosis.

SETTING: Inflammation-related oxidative stress has been implicated in the pathogenesis of lung fibrosis and dysfunction in patients with pulmonary tuberculosis. OBJECTIVE: To investigate the effects of antimicrobial chemotherapy and smoking status on the plasma concentrations of the anti-oxidative nutrients vitamin C, vitamin E and beta-carotene, as well as those of iron, lipid peroxides and the acute phase reactants C-reactive protein (CRP) and ferritin. DESIGN: A total of 41 patients with active pulmonary tuberculosis were studied at the outset and after 6 months of antimicrobial chemotherapy. RESULTS: Initial plasma concentrations of vitamin C and beta-carotene were low, returning to normal values after chemotherapy in the non-smokers, but not in the smokers, while those of vitamin E remained low throughout in both groups. Ferritin and CRP concentrations decreased significantly following chemotherapy, with the former higher in smokers than in non-smokers. Serum lipid peroxides were elevated in patients with pulmonary tuberculosis and were unaffected by chemotherapy or smoking habits, while iron levels were not significantly affected by chemotherapy. Although residual dysfunction and infiltration were evident, pulmonary function (FEV1) and radiographic score improved equally in both smokers and non-smokers following antimicrobial chemotherapy. CONCLUSIONS: Even after 6 months of apparently successful antimicrobial chemotherapy, pulmonary tuberculosis is associated with increased oxidative stress, which is unrelated to cigarette smoking and characterized by increased levels of circulating lipid peroxides and low concentrations of plasma vitamin E.

Clinical, radiographic and lung function features of diffuse congenital cystic adenomatoid malformation of the lung in an adult.

Congenital cystic adenomatoid malformation of the bronchi with bilateral lung involvement has only previously been reported in one possible adult case. This report describes a young man with bilateral diffuse lung involvement, characteristic histological features, and a mixed restrictive/obstructive lung function pattern.

The use of the flow-volume loop in assessing the results of laryngotracheal reconstruction.

The difficult problem of assessing pre- and postoperative airway function in patients with laryngotracheal upper airway obstruction is discussed. A series of 26 patients with various forms of this problem is presented. The method of performing the flow-volume loop (FVL) is described and the theory behind the investigation is reviewed. Five of the series of 26 patients are described in detail as examples, and the advantages and disadvantages of this investigation are discussed fully. The FVL appears to be the only really objective test to assist the laryngotracheal reconstructive surgeon. It is easily performed in most cases and should form part of the diagnostic and postoperative workup.