香港胸肺學會 美國胸肺學院港澳分會 Hong Kong Thoracic Society & ACCP (HK & Macau Chapter)

A Trimonthly joint communiqué of Hong Kong Thoracic Society & American College of Chest Physicians (Hong Kong and Macau Chapter)

聯合會員通訊

NewsletterNewsletterNewsletterNewsletter

Circulation restricted to members only

Volume 15 Number 3 • Sep / Oct 2005

VVVVontents

Council Members (2005-2007)

1 HKTS and ACCP (HK & Macau Chapter)

Editorial Board 2 Editorial

2 Instruction to contributors

Special Articles 3 Control of tobacco smoking in Hong Kong

5 Report smoky vehicles!

Clinical Meeting Summary 6 A man with muscle weakness and recurrent pneumonia

13 Persistent lung shadow in an “asymptomatic” female patient

17 A lady with recurrent chest infiltrates

20 Hazelnut icecream

Dissertation abstracts 24

Practical Corner 33 Questions for the next issue 34 What are the ways to diagnose latent tuberculous infection? 37 How do you work up a patient with suspected idiopathic interstitial

pneumonia? 40 What physical and aerodynamic properties of radon in making it an

important etiology of lung cancer? Medical Statistics Corner

41 Medical biostatistics

Book Review Column 47 High-resolution computed tomography of the lungs: a pattern

approach

Diary of International Conferences 48

Forthcoming Clinical Meetings 49

Useful Websites 50

Chest Full Text On-Line 51

Membership News 51

Funds and Grants 52

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Council of the Hong KongThoracic Society

Executive Committee of the American College of Chest Physicians (HK & Macau Chapter)

President Dr MOK Yun Wing, Thomas

Vice-President Dr TAM Cheuk Yin

Honorary Secretary Dr CHAN Wai Ming

Honorary TreasurerDr HO Chung Man, James

Council Members Prof HUI Shu Cheong, David

(Ex-President) Prof TSANG Wah Tak, Kenneth

Dr LAI Kei Wai, ChristopherProf LAM Wah Kit

Dr YAM Yin Chun, Loretta Dr CHAN Yuk Choi

Prof CHAN Mo Wah, Moira Dr YU Wai Cho

Dr PANG Joseph Dr HO Sheng Sheng

Dr YEE Kwok Sang, WilsonDr TSE Pak Yiu

Dr SO Kit Ying, Loletta Dr CHUI Wing Hung

Chief Editor:NewsletterDr KO Wai San, Fanny

Address for Correspondence Dr CHAN Wai Ming

Intensive Care Unit, Queen Mary Hospital Pokfulam, HK

President Dr WONG Poon Chuen

Vice-President Dr WONG Mo Lin, Maureen

Honorary Secretary/Treasurer Dr CHU Chung Ming

Executive Committee Members Dr CHAN Kin Sang (Ex-President) Prof LAM Wah Kit Dr CHAN Hok Sum Dr LAM Chak Wah Dr TAM Cheuk Ming Dr CHOO Kah Lin Dr CHAN Wai Man, Johnny Dr KWOK Kai Him, Henry Dr LAU Chun Wing

Governors Dr CHAN Chun Kwong, Jane Prof YIM Ping Chuen, Anthony Dr YEW Wing Wai

Regent Prof IP Sau Man, Mary

Address for Correspondence Dr CHU Chung Ming Department of Medicine, United Christian Hospital,Hong Kong

2 0 0 2 0 0 2 0 0 2 0 0 5555 ---- 2 0 0 2 0 0 2 0 0 2 0 0 7777

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XXXX ditorial Board

Editor Dr Fanny WS Ko

Deputy Editor Dr Johnny Chan

Board Members Dr Kah Lin CHOO

Dr James Ho Dr Sheng Sheng HO Dr Henry KWOK Dr Wai Kei LAM

Miss Barbara LAW Dr Loletta K Y SO

Dr Julie Wang Dr Matthew K Y WONG Dr Maureen M L WONG

Dr Wilson K S YEE

Address for Correspondence Dr Fanny WS Ko

Dept. of Medicine and Therapeutics Prince of Wales Hospital

Shatin N.T.

Hong Kong

Fax (852) 26375396

Email

fannyko@cuhk.edu.hk

Editorial I am sure that everyone would like to breathe in fresh and clean air rather than to breathe in air that is “polluted” by tobacco smoke and vehicle exhaust. We have two special articles in this issue of the newsletter, one on the control of environmental tobacco smoke in Hong Kong, and the other on how to report “smoky vehicles” to the regulatory authority.

Congratulations to the 7 respiratory trainees who have passed their exit examination in the specialty board of Respiratory Medicine in June 2005. We have compiled their dissertation abstracts in this issue of the newsletter so that our readers can appreciate their research work. In this issue of the newsletter, you can also find the reports of the clinical meetings by 4 different hospitals, namely Queen Mary Hospital, Ruttonjee Hospital, Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital. The practical corner and the medical statistic corner will continue to provide interesting and useful knowledge to our readers.

Instruction to Contributors

We welcome contributions from invited guests and members of the Hong Kong Thoracic Society and the American College of Chest Physicians (Hong Kong and Macau Chapter). Articles should be prepared with suitable word processing software (eg Word 2000). Figures, table, pictures and photo- micrographs should be saved in the same file. Please do not use the auto-indexing features. The file could be sent either by e-mail or by post (on a floppy disc or CD) to the Chief Editor. Please indicate to the Chief Editor if the material has to be returned after the editing process. The article would be printed in the same way as it is submitted. The accuracy of the materials published is the responsibility of the contributors. The contributors must ensure that the materials submitted do not infringe copyright.

Disclaimer

The opinions expressed in this newsletter are those of the author/s and do not necessarily reflect the official policies of the Hong Kong Thoracic Society, American College of Chest Physicians (Hong Kong and Macau Chapter), the institution with which the author(s) is/are affiliated, or the publisher.

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Control of Control of Control of Control of TTTTobacco obacco obacco obacco SSSSmoking in Hong Kongmoking in Hong Kongmoking in Hong Kongmoking in Hong Kong

Dr Fanny W.S. Ko and Prof. Moira Chan-Yeung

a Department of Medicine and Therapeutics, Prince of Wales Hospitalb University Department of Medicine, Queen Mary Hospital

Environmental tobacco smoke (ETS) exposure or passive smoking is a major source of indoor air pollution.1 ETS comes from both the sidestream smoke emitted from the smoldering tobacco and the mainstream smoke exhaled from the smoker. In fact, the sidestream smoke contains over 60 human carcinogens, such as nitrosamines, benzene, 4-aminobipheynyl and a wide variety of polycyclic aromatic hydrocarbons. The toxic substance in the sidestream smoke is fact very similar, if not less than, the ingredients in the mainstream smoke.1 ETS has many harmful effects on human. In adults, exposure to ETS is associated with increase risk of carcinoma of lung2-4 and cardiovascular diseases.5 In addition, exposure to ETS not only leads to a much higher rate of respiratory symptoms, like wheezing apart from cold, cough and sputum in never-smokers6, but also loss of small airway lung function in young adults (like those between 15 to 35 years old). A study by Masi MA et al found that a 20 year old non-smoking young male who lived at home with both smoking parents had a 800ml reduction in FEF 25-75 compared with another man of the same age without such exposure.7 In children, longitudinal studies had found that exposure to ETS was associated with a lower lung function.8 In addition, increased lower respiratory tract illness was noted in small children exposed to ETS.9, 10 In view of the harmful effects of ETS, the government of Hong Kong attempts to put in place some measures to control tobacco smoking in public places. The Tobacco Control office (TCO) under the Department of Health was established in February 2001 to enhance and coordinate the Government’s tobacco control efforts. The vision of the TCO is to “promote a smoke-free culture in Hong Kong so as to safeguard the health of the community”. 11 The priority functions of the TCO are as follows: 1. To educate and assist managers and staff of public premises to comply with and enforce the Smoking (Public Health) Ordinance (Cap. 371). 2. To screen printed tobacco advertisement materials. 3. To inspect tobacco retailers for tobacco advertisement, improper health warnings and signage, etc. 4. To conduct anti-smoking health education. 5. To enhance the smoking cessation service provided by the Department of Health. 6. To assist the Health, Welfare and Food Bureau in reviewing tobacco control policy and legislation. The TCO has been working hard to create a smokefree workplace. As most adults spend at least one-third of their time at work, a smokefree work environment will protect the lung health of the workers. The TCO has delivered a series of Smokefree Workplace Workshops regularly to assist companies and organizations to implement smokefree policy. The workshops are conducted in the TCO office or in company sites. The TCO has also produced the “Smoke-free Workplace Impl ementation Manual” in Chinese. Through this manual, one can learn practica l advice on how to establish and maintain a smoke-free environment in workplace.

pecial Article

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Furthermore, the TCO has put considerable efforts in arranging many anti-smoking activities via different channels. For example, the Tobacco Control Teams and Smoke-Free Ambassadors have been working jointly with the Police Training School and Education Department in providing anti-smoking trainings for adolescents. Shop-to-shop visits are being conducted in shopping malls and office buildings for health education . Apart from the TCO, the Department of Health also regularly conducts smoke cessation activities in various service units including chest clinics and elderly health centers. In order to further enhance smoking cessation services, the Department of Health has also introduced nicotine replacement therapy in the Education and Training Center in Family Medicine. Furthermore, a smoking cessation hotline 29618883 has been put into operation to assist smokers to quit the addiction. More information can be obtained from this website: http://www.tobaccocontrol.gov.hk/eng/loadframe.html?id=129 The Hong Kong Thoracic Society, the American College of Chest Physicians (Kong Kong & Macau Chapter) and the Hong Kong Lung Foundation strongly support the Government on tobacco smoking control in the community. In response to Government’s proposed legislative amendment of Smoking (Public Health) Ordinance, these three local chest organizations had organized a press conference on March 20, 2005 to emphasize the harmful effects of ETS on lung health and to voice their strong support to the proposed legislative amendment.

References: 1. Chan-Yeung M, Dimich-Ward H. Respiratory health effects of exposure to environmental tobacco smoke.

Respirology 2003;8:131-9. 2. Wang L, Lubin JH, Zhang SR, Metayer C, Xia Y, Brenner A, Shang B, Wang Z, Kleinerman RA. Lung cancer

and environmental tobacco smoke in a non-industrial area of China. Int J Cancer 2000;88:139-45. 3. Behera D, Balamugesh T. Indoor air pollution as a risk factor for lung cancer in women. J Assoc Physicians

India 2005;53:190-2. 4. Bartal M. Health effects of tobacco use and exposure. Monaldi Arch Chest Dis 2001;56:545-54. 5. Leone A. Relationship between cigarette smoking and other coronary risk factors in atherosclerosis: risk of

cardiovascular disease and preventive measures. Curr Pharm Des 2003;9:2417-23. 6. Leuenberger P, Schwartz J, Ackermann-Liebrich U, Blaser K, Bolognini G, Bongard JP, Brandli O, Braun P,

Bron C, Brutsche M, et al. Passive smoking exposure in adults and chronic respiratory symptoms (SAPALDIA Study). Swiss Study on Air Pollution and Lung Diseases in Adults, SAPALDIA Team. Am J Respir Crit Care Med 1994;150:1222-8.

7. Masi MA, Hanley JA, Ernst P, Becklake MR. Environmental exposure to tobacco smoke and lung function in young adults. Am Rev Respir Dis 1988;138:296-9.

8. Tager IB, Munoz A, Rosner B, Weiss ST, Carey V, Speizer FE. Effect of cigarette smoking on the pulmonary function of children and adolescents. Am Rev Respir Dis 1985;131:752-9.

9. Fergusson DM, Horwood LJ. Parental smoking and respiratory illness during early childhood: a six-year longitudinal study. Pediatr Pulmonol 1985;1:99-106.

10. Chen Y, Li W, Yu S. Influence of passive smoking on admissions for respiratory illness in early childhood. Br Med J (Clin Res Ed) 1986;293:303-6.

11. Tobacco Control office of Hong Kong. http://www.tobaccocontrol.gov.hk/eng/loadframe.html?id=1.

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pecial Article

Report Report Report Report Smoky Vehicles!Smoky Vehicles!Smoky Vehicles!Smoky Vehicles!

Dr. CM Chu

Department of Medicine and Geriatrics, United Christian Hospital

Why is it important to report smoky vehicle? Increase in air pollution levels is known to be associated with: - increase overall mortality and mortality due to heart and lung diseases - lower life expectancy - increase hospitalisation due to lung diseases - reduction in lung function - exacerbation of asthma Diesel vehicles are the primary cause of street level pollution and acute pollution in urban areas of Hong Kong. The worst offenders are big buses, heavy goods vehicles, passenger vans and light goods vehicles. The city has over 500,000 vehicles with about 150,000 powered by diesel. Diesel emissions account for nearly 98% of respirable suspended particles and 80% of nitrogen dioxide emitted by all vehicles. Diesel particulate matter has long been recognised as harmful to health. As experts in Respiratory Medicine in Hong Kong, we should take a leading role in reducing air pollution. You can now help reduce air pollution in HK by reporting smoky diesel vehicles on-line. What can you do to help? 1. Spot smoky vehicles while you are driving 2. With a mini-voice recorder, note down their car plate numbers, date of spotting, type of vehicles and street 3. Report to the Environmental Protection Department at the following site:

https://epic.epd.gov.hk/ca/uid/smoky_public 4. On receiving your complaint report, they will:

- check the concerned vehicle registration record, and - if the vehicle registration is valid, send the concerned vehicle owner a warning letter asking him/her to check smoke emission of the vehicle.

Start reporting today!

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linical Meeting Summary

A A A A MMMMan with an with an with an with MMMMuscle uscle uscle uscle WWWWeakneseakneseakneseakness ands ands ands and RRRRecurrecurrecurrecurrent ent ent ent PPPPneumonianeumonianeumonianeumonia

Dr Julie KL Wang, Dr. Simon KS Ip, Dr. James CM Ho

University Department of Medicine, Queen Mary Hospital

Case History The patient was a 67- year old retired truck driver with good past health, who lived in China with his family. He was a non-smoker and non-drinker with no known drug allergy history. He presented with fever and cough in the end of September, 2003 while staying in Guangdong. Before he came back to Hong Kong, he had been treated in China with intravenous cefepime and subsequently imipenem for 2 weeks. As he was also found to have low platelet count, intravenous immunoglobulins, dexamethasone and platelet transfusion had been given. He returned to Hong Kong in mid of October, 2003, still suffering from shortness of breath and low grade fever. Physical examination revealed bilateral basal coarse crepitations with otherwise normal findings. Chest radiograph showed bibasal and subpleural interstitial infiltrates (Figure 1) , while HRCT thorax demonstrated subpleural and peribronchial consolidation, interlobular septal thickening and ground glass appearance predominantly in the basal and periphery regions of both lung fields (Figure 2). Platelet count was 50, other blood count, renal and liver functions were normal. Arterial blood gas showed hypoxia. Sputum grew xanthomonas maltophilia, AFB smear was negative. Tests for HIV, coronavirus and immune markers were also negative. Bone marrow examination was normal. Spirometry showed restrictive defects with impaired diffusing capacity.

Figure 1. CXR on first presentation showing bibasal and subpleural interstitial infiltrates.

Figure 2. HRCT thorax on first presentation, here shows features of subpleural and peribronchial consolidation, interlobular septal thickening and ground glass appearance predominantly in the basal and periphery regions of both lung fields

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A course of intravenous timentin was started and the patient was referred for open lung biopsy as there was no improvement. Histology of the lung biopsy showed airspaces plugged with pale myxoid granulation tissue forming spherical polyps and short bundles, consistent with bronchiolitis obliterans organizing pneumonia (BOOP) (Figure 3).

Prednisolone 50mg daily was started in mid of November, 2003. There was remarkable resolution of pulmonary shadows from both CXR and HRCT thorax (Figure 4 & 5).

Steroid was tapered down to 20mg daily within 8 weeks’ time . Thereafter, the patient developed low grade fever and shortness of breath. Increased bibasal ground glass shadows was noted in chest radiograph (Figure 6). At the same time, there was mild proximal muscle weakness with creatine phosphokinase (CPK) elevated to ~1200U/L, facial rash was also noted. Vasculitic markers like ANCA, Anti-ENA, anti-Jo 1 antibodies were negative, HRCT thorax showed resolving peribronchial consolidation at the basal zone, and there was more ground glass opacities , interlobular septal thickening and traction bronchiectasis resembling pattern of non-specific interstitial pneumonitis (NSIP) ( Figure 7).

Figure 3. Histology showed airspaces at the centre of field are plugged with pale myxoid granulation tissue forming spherical polyps and short bundles. Some residual alveoli are seen outside this area.

Figure 4. CXR post steroid treatment Figure 5. HRCT thorax post steroid treatment

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This condition was compatible with relapse of BOOP with elements of NSIP and underlying dermatomyositis. Hence, prednisolone was stepped up to 50mg daily once again, coupled with intavenous tazocin to cover for possible infective elements. Despite these treatment, there was still intermittent fever, with both radiological and respiratory worsening (Figure 8). Fibreoptic bronchoscopy and bronchioalveolar lavage (BAL) was performed , which found pneumocystis carinii (PCP); cytomegalovirus (CMV) early antigen detection was positive from BAL and CMV pp65 antigenaemia showed 1 pos/ 2x105 WBC. Standard intravenous septrin therapy was given and steroid continued for PCP infection. Followed by septrin prophylaxis and steroid tapering in the subsequent 3 weeks. Apparently, the clinical condition improved . Malignancy screening including nasal biopsy, Epstein bar virus (EBV)-IgA, alpha fetal protein, carcinoembryonic antigen, prostate specific antigen and carbohydrate antigen 19.9, CT abdomen and pelvis were all negative.

Figure 6. CXR on first relapse, with increasing bibasal ground glass shadows

Figure 7. HRCT thorax on first relapse showing resolving peribronchial consolidation at the basal zone, however, there was more ground glass opacities, interlobular septal thickening and traction bronchiectasis resembling pattern of non-specific interstitial pneumonitis (NSIP)

Figure 8. Persistent fever and radiological deterioration despite stepping up steroid

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In mid of May, 2004, the patient complained of severe exertional dyspnoea with thick whitish sputum , he was taking prednisolone 20mg daily at that juncture and was intubated and admitted into ICU (Figure 9). Sputum culture, AFB smear, CMV pp65 antigenaemia and BAL culture were negative. Echocardiography showed satisfactory LVEF ~ 55%. HRCT thorax revealed increase in coarse reticular shadowings, ground glass attenuations and interlobular septal thickening were seen involving both lungs predominantly in bilateral lung bases. Disease progression was apparent as compared with previous study in March 2004 (Figure 10).

Intravenous methylprednisolone 60mg Q12H and cyclophosphamide was started for second relapse of BOOP/NSIP. Surveillance for CMV pp65 antigenaemia detected 24 pos/ 2x105 WBC upon high dose immunosuppression, although there was no clinical CMV disease. Pre-emptive treatment for CMV reactivation with ganciclovir was given for 3 weeks according to microbiologist recommendation. He improved subsequently and was maintained on cyclophosphamide 50mg daily while methylprednisolone was tapered to 16mg daily upon discharge (Figure 11 & 12).

Figure 9. CXR on second relapse Figure 10. HRCT thorax in second relapse

Figure 11. Disease in remission after cyclophosphamide and steroid treatment

Figure 12. Disease in remission, with residual bibasal fibrosis, interlobular septal thickening and traction bronchiectasis

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Discussion: Reported incidence of interstitial lung diseases (ILD) in polymyositis (PM) and dermatomyositis (DM) has been highly variable. Ten percent of the patients in 2 large series, each of which studied more than 100 PM/DM patients, were identified to have pulmonary infiltrates by roentgenographic criteria.1, 2 On the other hand, Songcharoen et al 3 , found that 7 of 15 (47%) cases had radiographic evidence of ILD in PM/DM, while Dickey and Myer 4 found that 12 of 42 (28.6%) cases with PM/DM were shown to possibly have ILD radiographically or by pulmonary function test results. ILD's occurrence has adverse impact on the prognosis of patients with PM/DM. Arsura et al 5, in a study of 67 patients with PM/DM and ILD, found a mortality rate of 40% after a period of 31 ± 32 months. Progressive ILD was the immediate cause of death in 58% of those who died. Marie et al 6, in a study of 55 PM/DM patients, identified a subgroup of 9 patients who developed ILD with a mortality rate as high as 22%, after a mean follow up of 70 ± 36 months. This mortality was significantly higher than those who did not have concomitant ILD (9%). The pattern of lung diseases in PM/DM is summarized below _____________________________________________________________________ Interstitial lung diseases Bronchiolitis obliterans organising pneumonia (BOOP) Usual interstitial pneumonia (UIP) Non-specific interstitial pneumonia (NSIP) Diffuse alveolar damage (DAD) Pulmonary capillaritis Pulmonary hypertension Primary vasculopathy Secondary to chronic heart or respiratory failure Infective pneumonitis Aspiration pneumonia Secondary to immunosuppressive agent Respiratory musculature dysfunction ________________________________________________________________________

Tazelaar et al 8 subclassified 14 open lung and 1 autopsy tissue biopsies and identified 6 BOOP, 5 usual interstitial pneumonia (UIP), 1 cellular interstitial pneumonia (CIP, which on subsequent review was found to be compatible with NSIP 9) and 3 diffuse alveolar damage (DAD). In this study, patients with BOOP were found to have a better outcome than UIP, while those patients with DAD had 100% mortality rate and the authors concluded that histological features were good predictors of survival. The frequency of occurrence of various ILD varies in different studies. Douglas et al 10 identified 70 patients with both ILD and either PM or DM. In that cohort, 22 patients underwent surgical biopsies and 18 of them had NSIP while 2 patients had DAD, 1 each had BOOP and UIP respectively. Schwarz et al, in an analysis of 6 cases of ILD in PM and DM7, found that 3 of their patients had a histological combination of organizing pneumonia in addition to interstitial pneumonitis. In one of these cases, they were able to demonstrate evolution of the inflammatory process to fibrosis with honeycombing and interstitial ossification (an autopsy finding). In another patient, follow-up lung biopsy demonstrated clearing of the inflammatory process with residual interstitial fibrosis. It underlines that there is a histological stage in PM/DM pulmonary disease where features of both fibrosing alveolitis and organizing pneumonia coexist. This might represent a "progressing" single disease rather than 2 distinct patterns and thus a good outcome is not invariable in PM/DM patients with organizing pneumonia.

The clinical features of PM/DM has been described elsewhere. Females with PM or DM are more likely to develop ILD, and the mean age at presentation is 50 years. On physical

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examination basilar crackles are commonly recorded 7 while finger clubbing is uncommon, and is different from cryptogenic fibrosing alveolitis (70%). ILD can appear concomitantly with, follow, or precede the appearance of muscle disease. Attempts had been made to correlate clinical presentations and behaviour of ILD with histopathological patterns.11 Patients presenting with acute respiratory symptoms with or without muscle or skin manifestations may have underlying DAD, BOOP or pulmonary capillaritis. While DAD can run a clinical course similar to the Hamman-Rich syndrome, where the prognosis is poor, BOOP and pulmonary capillaritis are often responsive to treatment with steroids. Those who present with asymptomatic radiographic infiltrates or chronic progressive symptoms in known cases of PM/DM may have underlying UIP or cellular IP (NSIP). The aetiology and pathogenesis of ILD in PM and DM remains to be uncertain. An infective association has been considered and agents such as EBV, CMV, hepatitis C infection had all been investigated but none was found to have a definite causal relationship. An immunological contributing factor is a possibility. Autoantibodies which bind to intracellular antigens are commonly detected in patients with inflammatory myopathies. Such autoantibodies are detectable by indirect immunofluorescence or immunodiffusion. Among these intracellular/autoantigens, the aminoacyl transfer ribonucleic acid (tRNA) synthetases, a group of enzymes involved in the binding of amino acids to their tRNAs, and their corresponding antibodies are thought to be of importance.12 There are six anti-aminoacyl tRNA synthetase antibodies (AAs) known and antihistidyl tRNA synthetase (anti Jo-1) was the first of these AAs to be discovered, and is the most common. It is found in around 25% of patients with myositis overall, more commonly in PM than DM. About 50-80% of patients with anti-Jo-1 eventually develop myositis and ILD. Antithreonyl tRNA synthetase (anti-PL-7) and antialanyl tRNA synthetase (anti-PL-12) antibodies are less commonly found in PM/DM (3-4%). Autoantibodies to isoleucyl-tRNA synthetase (anti-OJ), glycyl-tRNA synthetase (anti-EJ), and asparaginyl-tRNA synthetase (anti-KS) are the least common, occurring in less than 2%. The pathogenic relevance of the antisynthetase antibodies found in PM/DM patients is uncertain. No report of preferential disposition of such antisynthetase antibodies in the lung lesions had been found. The binding of antibodies in the sera of different PM/DM patients to different epitopes in the synthetase molecules suggest antisynthetase activity as a cross reacting antibody stimulated by environment. Therapeutic options and their pros and cons must be discussed in detail with the patients and the physician must identify those with "potentially reversible disease" as opposed to those who are unlikely to respond. The rationale for long term treatment in the hope of achieving symptomatic/objective clinical improvement or stability needs to be explained carefully. Corticosteroids alone have been the empirical treatment of choice for/subjective PM/DM with or without ILD. Steroid-resistant ILD is defined as disease progression despite administration of prednisolone. Under such circumstances, various immunosuppressive agents such as azathioprine, methotrexate, cyclophosphamide, each of them with specific adverse effect profiles 13, were reported to have favourable efficacy.14,15 Azathioprine or methotrexate, in combination with corticosteroid may be as efficacious as cyclophosphamide but no formal comparison has been made amongst them. Nawata et al studied a cohort of 36 with ILD out of 111 PM/DM patients and further subdivided them into groups with either raised or normal serum CPK at the onset of ILD (for the latter group the patients fulfil all the other diagnostic criteria for PM/DM together with a raised serum aldolase level).16 They found that DM patients without CPK elevation at the onset of myositis developed ILD at a higher frequency (62.5%) than PM/DM patients with elevated CPK levels. All the patients were initially treated with

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corticosteroids, and while the therapy was fairly effective on rashes in DM and in treating muscle symptoms, 16 steroid-resistant ILD patients were identified. These were mostly from the group of patients who had normal CPK at the onset of ILD. Eleven of these 16 patients died from respiratory failure despite the addition of pulsed methylprednisolone therapy. The 5 remaining steroid-resistant ILD patients were treated with prednisolone and cyclosporin. Clinical deterioration was prevented in all these 5 patients. Cyclosporine, an immunosuppressive agent used widely in post organ transplantation, is known to preferentially suppress T cell activation, which might suggest a role of activated T cells in the pathogenesis of steroid resistant ILD in PM/DM. Tacrolimus, a T-helper cell inhibitor, was reported to be effective in treatment of refractory PM. Oddis et al studied a group of 8 patients whose myositis had failed to respond to corticosteroids and at least one of the immunosuppressive agents given concomitantly.17 Six of these patients were anti-Jo-1 antibody positive, 5 of whom had radiologic evidence of parenchymal interstitial infiltrates. After receiving oral tacrolimus, 3 patients were noted to have responded favourably by pulmonary function measurements. The response in this group of PM patients is probably not too surprising since it is a predominantly cell mediated disease.

References 1. Salmeron G, Greenberg SD, Lidsky MD et al. Polymyositis and diffuse interstitial lung disease. A review of the

pulmonary histopathologic findings. Arch Intern Med 1981;141:1005-1010. 2. Medsger TA, Robinson H, Masi AT et al. Factors affecting survivorship in polymyositis. A life-table study of 124

patients. Arthritis and Rheumatism, 1971, Vol. 14, No. 2, 249-258. 3. Songcharoen S, Raju SF, Pennebaker JB. Intertsitial lung disease in polymyositis and Dermatomyositis. J

Rheumatol 1980;7:353-60 4. Arth Dickey BF, Myers AR. Pulmonary disease in polymyositis/dermatomyositis. Semin Rheum 1984;14:60-76. 5. Marie I, Hatron PY, Hachulla E et al. Pulmonary involvement in polymyositis and dermatomyositis. The Journal of

Rheumatology 1998; 25:7 1336-1339. 6. Asura EL, Grennberg AS. Adverse impact of interstitial pulmonary fibrosis on prognosis in polymyositis and

dermatomyositis. Seminars in Arthritis and Rheumatism, 1988;18: 29-37 7. Schwarz MI, Matthay RA, Sahn SA et al. Interstitial lung disease in polymyositis and dermatomyositis: Analysis of

six cases and review of the literature. Medicine 1976 55:89-104. 8. Tazelaar H, Viggiano RW, Pickersgill J et al. Interstitial lung disease in polymyositis and dermatomyositis: Clinical

features and prognosis is correlated with histological findings. Am Rev Respir Dis 1990,14:727-7333. 9. Katzenstein A, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histological Features and clinical

significance. Am J Surg Patho 1994;18:136-47. 10. Douglas WW, Tazelaar HD, Hartman TE et al. Polymyositis-dermatomyositis-associated interstitial lung disease.

Am J Respir Crit Care Med. 2001;164:1182-5. 11. Schwarz MI. The lung in polymyositis. Clinics in Chest Medicine 1998;19:701-712. 12. Hirakata M, Nagai S. Interstitial lung disease in polymyositis and dermatomyositis. Current Opinion in

Rheumatology 2000;12:501-508. 13. Imokawa S, Colby TV, Leslie KO et al. Methotrxate pneumonitis: review of the literature and histopathological

findings in nine patients. Eur Respir J 2000;15:373-381. 14. Rowen AJ, Reichel J. Dermatomyositis with lung involvement, successfully treated with azathioprine. Respiration

1983;44:143-146. 15. Al-Janadi M, Smith CD, Karch J. Cyclophophosamide treatment of interstitial pulmonary fibrosis in

polymtositis/dermaomyositis. J Rheumatol 1989,16:1592-1596. 16. Nawata Y, Kurasawa K, Takabayashi K et al. Corticosteroid resistant interstitial pneumonitis in

dermatomyositis/polymyositis: Prediction and treatment with cyclosporin. The Journal of Rheumatology. 1999;26: 1527-1533.

17. Oddis CV, Sciurba FC, Elmagd KA, Starzi TE: Tacrolimus in refractory polymyositis with interstitial lung disease. Lancet 1999, 353:1762-1763.

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linical Meeting Summary

Persistent Persistent Persistent Persistent LLLLung ung ung ung SSSShadow in an “hadow in an “hadow in an “hadow in an “AAAAsymptomatic” symptomatic” symptomatic” symptomatic” FFFFeeeemale male male male PPPPatient atient atient atient

Dr. KW Chan, Dr. SW Yan, Dr. CF Wong

Tuberculosis and Chest Unit Grantham Hospital

Case history

A 40-year-old part-time cleansing worker, non-smoker and non-drinker with unremarkable past health was found to have chest X-ray (CXR) abnormality with a left upper zone shadow (Figure 1) since 1994. She received 2 courses of anti-tuberculous treatment in 1994 and 1997 respectively for suspicion of tuberculosis on radiological ground but without any bacteriological or histological proof. However, the lung shadow persisted despite treatment. Figure 1 Chest X-ray at presentation showing left upper zone shadowing She was admitted to Grantham Hospital in 1999 for further management. Physical examination was unremarkable. Her complete blood count was normal and erythrocyte sedimentation rate was only 7 mm/hour. Sputum examination was negative for pyogenic organisms, fungi, acid-fast bacilli and malignant cells. Serial CXRs showed a persistent left upper zone shadow with well-defined border and homogenous content which fluctuated in size. Computed Tomography (CT) examination of thorax showed a cyst-like lesion in left upper lobe with probably fluid content. Percutaneous transthoracic needle biopsy was done in November 1999 and it yielded 10 ml of greyish pus-like fluid. Examination of the aspirated fluid showed presence of Aspergillus on staining and culture (Figure 2).

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Figure 2 Pathological examination of the needle aspirate

A course of anti-fungal treatment in the form of amphotericin B was given and followed by itraconazole. Repeated CT thorax after 3 months of itraconazole therapy showed slight decrease in size of the left upper lobe fluid-filled cyst-like lesion. However, a repeated needle aspirate still yielded pus-like fluid, which was positive for Aspergillus on staining and culture. Thoracotomy was suggested but the patient refused surgery. Itraconazole was continued for a total of 6 months and stopped. The patient was well throughout the treatment with no respiratory symptoms at all. She was then regularly followed up. In 2003, she started to have several bouts of cough with expectoration of greyish sputum. CXR and CT thorax showed new fine patchy infiltrates over the left lower lobe apart from the persistent left upper zone lesion (Figure 3). Clinical suspicion of spillage of Aspergillus-infected material to the left lower lobe was raised. Another course of itraconazole was started to cover the possible Aspergillus infection of the left lower lobe. Subsequent CXR and CT thorax showed resolution of the left lower lobe infiltrates.

A B C Figure 3 Chest X-ray (A) and CT thorax ( B) taken in 2003 showing persistent left upper zone shadowing with fine infiltrate over the left lower lobe

H & E staining showing necrotic debris and inflammatory cells

Grocott staining showing slender septated hyphae, consistent with aspergillus infection

15

The patient finally agreed for surgery. Video-assisted thoracoscopic surgery (VATS) with left upper lobectomy was done in 2005. Gross examination of the resected left upper lobe showed a 5cm x 4.5cm x 3cm cavity with thick brownish lining, with the lung surrounding the cavity being consolidated. There was no gross communication between the cavity and the bronchial tree. Microscopic examination of the section of the lung showed an ectatic bronchus with intact epithelial lining and mild non-specific chronic inflammation of the walls. Surrounding lung showed florid organizing inflammation with no evidence of Aspergillus infection of the surrounding lung tissues. Diagnosis: This patient was suffering from Aspergillus lung infection but it did not fit into any of the usual or well-described forms of Aspergillus lung disease. This patient had a blocked persistent cavity in the left upper lobe with fluid content infected with Aspergillus. On review after extensive search of the medical literature, this condition fits into an entity described by Rzepecki W, et al, 1,2 in 1978 as “tumour-like blocked pulmonary cavities with liquid content infected with aspergilli."

Discussion: Aspergillus is a ubiquitous soil-dwelling organism found in decay matters like organic debris, dust, food and rotted plants. There are around twenty species among the genus which have been reported as causative agents of opportunistic infections in human beings. It is usually acquired by inhalation of the air-borne spores from inanimate sources. It grows best at 37°C and the spores can be deposited deep in the lungs and causes a variety of clinical syndromes. There are several well-described forms of Aspergillus related lung disease shown in figure 4.3

Inhalation of aspergillus spores

Colonization

Normal host Cavitary Lung disease

Asthma ICH Chronic lung disease

or mild ICH

NoSequel Aspergilloma

ABPAInvasive

Pulmonaryaspergillosis

Chronic necrotizingaspergillosis

Figure 4. Aspergillus related lung disease ICH = immunocompromised hosts; ABPA = allergic bronchopulmonary aspergillosis. Modified from Chest 2002;121:1988-1999.

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In normal host, colonization of Aspergillus can result in no sequel. However in other patients, manifestations may vary in patients with different underlying pulmonary or host conditions. For instance, Aspergillus may colonize and grow in a pre-existing lung cavity forming a fungal ball known as ‘aspergilloma’. Allergic bronchopulmonary aspergillosis (ABPA) may occur with the disease manifested as an allergic response to the fungal spores in patients with underlying bronchial asthma. In chronic necrotizing pulmonary aspergillosis (CNPA), Aspergillus can invade the lungs of patients with chronic lung disease or those with mild impairment of immune defence mechanism. In immunocompromised patients, invasive pulmonary aspergillosis (IPA) can occur and other organ involvement may be evident as well. Our patient was a middle-aged female who had neither underlying systemic illness nor chronic local lung disease. She was not immuno-compromised and was not on any regular medications. Clinically, she was asymptomatic at presentation and only at her later stage of the disease when she experienced intermittent bouts of greyish expectoration without any haemoptysis, chest pain or constitutional upset. Her immuno-competent status spoke against invasive pulmonary aspergillosis which commonly occurred in patients with prolonged neutropenia, in those who have received organ transplantation or cytotoxic chemotherapy, etc. The radiological presentation was a well-defined homogenous opacity that emptied and reformed. The absence of fungal ball with air-crescent in a pre-existing cavity made it not typical of aspergilloma. There were also no features of allergic reaction that accompanied ABPA and Aspergillus-related hypersensitivity pneumonitis. The mass shadow only contained fluid substance and no communication with the surrounding lung or vessel permeation can be found. This “non-invasiveness” was rather different from CNPA and IPA in which some extent of invasion was needed to substantiate the diagnoses. Rzepecki W, et al, 1,2 in 1978 reported exactly the same clinical scenario in his case-series of ten patients. The condition was described as tumour-like blocked pulmonary cavities with liquid content infected with aspergilli, TBLA in short. As the name implied, the author highlighted its four characteristics. Firstly, it appeared as a tumour- like mass on CXR before operation (CT scan was not readily available in the seventies). Secondly, it was a pulmonary cavity with blocked bronchus which was responsible for the round or oval shape of the distended cysts and their sharp contours and homogenous shadowing on CXR. Thirdly, it contained liquid content and lastly the liquid invariably grew Aspergillus. All the cases reported underwent operation with the condition confirmed with operative findings. There were no further publications on this type of manifestation of Aspergillus lung disease in the literature, written in English at least, to our knowledge. Its natural course, prognosis and approach in management were not known due to the rarity in its own right. To conclude, Aspergillus is a ubiquitous organism which can cause infection in humans with a wide spectrum of manifestation. From non-allergic to allergic, saprophytic to invasive and airway-predominant to parenchyma-predominant, its classification often overlaps and its description made multifaceted. TBLA presents itself rather interestingly and uniquely. Whether it is a rare form of aspergilloma or a distinct form of Aspergillus infection needs further exploration. Its exact position in the classification web is not well defined.

References 1. Rzepecki W. A trial of isolating a tumor-like form of pulmonary cavities infected with aspergilli: I. Preoperative

data, diagnostic difficulties. Bronchopneumologie 1978; 28:1-11. 2. Rzepecki W, Harazda M, Dolezal M. A trial of isolating a tumor-like form of pulmonary cavities infected with

aspergilli; II. Intra- and postoperative, morphologic and serologic data. Bronchopneumologie 1978; 28: 87-98. 3. Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest 2002; 121: 1988-1999.

17

linical Meeting Summary

A A A A LLLLady with ady with ady with ady with RRRRecurrent ecurrent ecurrent ecurrent CCCChest hest hest hest IIIInfiltratesnfiltratesnfiltratesnfiltrates

Dr Michael CH Chan, Dr. Fanny WS Ko, Dr. David SC Hui

Department of Medicine and Therapeutics,

Prince of Wales Hospital

Case history The patient was a 40 year-old lady with good past health who presented with 1 month history of cough, whitish sputum and weight loss of 1lbs. The symptoms persisted despite antibiotics treatment prescribed by the general practitioner. Physical examination did not reveal any abnormality. Blood tests were unremarkable with normal complete blood picture, renal and liver function, except that the antinuclear antibody was slightly raised (titre 1:40). Her simple spirometry was normal but her chest radiography (CXR) showed left middle zone peripherally located consolidation (Figure 1). Bronchoscopy was performed but revealed no endobronchial lesions and examinations of the bronchoalveolar lavage, including routine culture, test for acid fast bacilli and cytology, were all negative. Computer tomography of chest showed patchy consolidation at the left lingular segment, left lower lobe and right upper lobe. The patient was referred to the cardiothoracic surgeon and VATS lung biopsy of the left lower lobe was performed. Histology of the biopsy showed multi-focal peribronchial non-caseating granulation tissues and multinucleated giant cells. Microbiological tests of the biopsy specimen were negative. A diagnosis of bronchiolitis obliterans-organizing pneumonia (BOOP) was made. Systemic steroid (prednisolone 0.75 mg/kg/day) was started with a gradual tapering dose over the following 6 months. Repeat CXR after steroid therapy showed resolution of the lung shadows (Figure 2).

Figure 1. CXR before systemic steroid Figure 2. CXR after systemic steroid

The patient developed increasing cough and infiltrates on CXR upon stopping of the 6 months course of systemic steroid therapy. As she refused further investigations including bronchoscopy or lung biopsy, she was first treated with a course of antibiotic for suspected infection. Her sputum was negative for micro-organisms or cytology. As her symptoms showed no response to antibiotics, she was treated as recurrence of BOOP with systemic steroid. Her symptoms improved quickly with resolution of lung infiltrates on CXR upon initiation of steroid. However the patient developed cough again upon tapering of steroid over 6 months. She was treated with a total of 4 courses of systemic steroid (6

18

to 9 months each time) due to the recurrence of cough and chest infiltrates. On every occasion, she responded to systemic steroid well and patient refused further invasive investigations (including bronchoscopy and VATS lung biopsy). After the third course of systemic corticosteroid, she developed right parotid swelling and left cervical lymphadenopathy. She was thus referred to the ENT surgeon. However, before she was seen, the swelling and lymphadenopathy subsided spontaneously. In early 2005, she self detected left axillary’s lymphadenopathy for a few weeks without respiratory or constitutional symptoms. CT scan of thorax, abdomen & pelvis was performed and multiple enlarged lymph nodes (size ranged from 2-5 cm in diameter) found in the thoracic and para-aoritc area (Figure 3). Fine needle aspiration (FNA) of left axillary lymph node was performed but it was non-diagnostic. Excision biopsy of left axillary lymph notes was thus performed which showed features compatible with non-Hodgkin lymphoma (diffuse large B cell lymphoma)(Figure 4). On looking back, the patient is likely to have suffered from BOOP, with underlying lymphoma which declared itself as the primary cause with time

Figure 3. CT abdomen Figure 4. Immunohistochemical stain of the

axillary lymph node. Brown colour represented positive stain for CD 20.

Discussion There are several forms of pulmonary manifestations of lymphoma. Firstly, the pulmonary lesion is the result of haematogenous dissemination of Hodgkin lymphoma. Secondly, the lung involvement is due to contiguous invasion from a hilar or mediastinal site of the nodal lymphoma . Finally, the pulmonary lesions can present as the primary pulmonary manifestation of lymphoma. The clinical features may include mediastinal lymphadenopathy, lung parenchymal disease, pleural effusion, chylothorax, or primary pleural lymphoma.1 From the literature, there was only 1 study reporting that BOOP and lymphoma presenting together2. There was no information in the literature to suggest the causal relationship between BOOP and lymphoma. Radiological feature may help to identify a patient with BOOP with underlying lymphoma. The CXR at presentation in patients with hematological spread of lymphoma to the lungs is more likely to have diffuse infiltrates (67%) than having nodular or mass-like lesions (22%)3. In most cases, symptoms and lung function test results are non-specific and are not useful to differentiate whether a patient with BOOP has underlying lymphoma.3

19

There are also some investigations other than radiological feature which can help differentiating between primary BOOP or BOOP secondary to lymphoma. The presence of atypical lymphocytic infiltrate in open lung biopsy specimen is more suggestive of BOOP secondary to lymphoma.4 Patients with BOOP secondary to lymphoma are more likely to require higher dose of steroid to control the pulmonary infiltrates and relapse is more frequent upon tapering dose of steroid when compared to primary BOOP.5

Furthermore, other associated symptoms like mononeuritis multiplex, Gullian Barre Syndrome are more likely to occur in cases with BOOP secondary to lymphoma than in primary BOOP.6 There are several treatment options for pulmonary involvement of lymphoma7 1. Observe 2. Chemotherapy 3. Localised radiation therapy 4. Autologous stem cell transplant 5. Anti-CD20 monoclonal antibody e.g. rituximab There is very limited information on the prognosis of patients suffering from both BOOP and lymphoma. Generally speaking, patients with secondary BOOP (related to other diseases) had a higher mortality rate when compared to primary BOOP. The disease prognosis tends to be more related the underlying conditions.8

Conclusion There are limited published data about the concomitant presentation of BOOP and lymphoma. The relationship between BOOP and lymphoma remains elusive. BOOP & lymphoma may be interrelated. The diagnosis of BOOP is made by exclusion and one needs to watch out for secondary cause especially in cases that are resistant to standard treatment with systemic steroid.

References 1. J. Cadranel, M. Wislez, and M. Antoine et al. Primary pulmonary lymphoma. European Respiratory Journal

2002;20:750-762. 2. White DA, Wong PW, Downey R et al. The utility of open lung biopsy in patients with hematologic malignancies.

Am J Respir Crit Care Med 2000;161(3 Pt 1):723-729. 3. M. Mokhtari, P. B. Bach, P. A. Tietjen and D. E. Stover et al. Bronchiolitis obliterans organizing pneumonia in cancer:

a case series. Respiratory Medicine 2002;96:280-286. 4. Hanawa T, Chiba W, Fujimoto T et al. T cell lymphoma presenting as recurrent bilateral pulmonary infiltrates over

five years. Japanese Journal of Thoracic Diseases 1996;34:363-368. 5. Lazor R, Vandevenne A, Pelletier A et al. Cryptogenic organizing pneumonia . Characteristics of relapses in a series

of 48 patients. Am J Respir Crit Care Med 2002;162: 571-577. 6. Safadi R, Berkman N, Haviv YS et al. Primary non-Hodgkin's lymphoma of the lung presenting as bronchiolitis

obliterans organizing pneumonia. Leuk Lymphoma 1997;28:209-213. 7. Seymour JF. New treatment approaches to indolent non-Hodgkin's lymphoma. Semin Oncol 2004; 31(1 suppl 2):27-

32. 8. Lohr RH, Boland BJ, Douglas WW, et al. Organizing pneumonia. Features and prognosis of cryptogenic, secondary,

and focal variants. Arch Intern Med 1997;157:1323-1329.

20

linical Meeting Summary

Hazelnut Hazelnut Hazelnut Hazelnut IIIIcecream cecream cecream cecream

Dr. YT Lo and Dr. HS Chan

Department of Medicine, Alice Ho Miu Ling Nethersole Hospital

Case summary A 59 year old gentleman with hyperlipidaemia on dietary control and Parkinson’s disease on Madopar, was admitted to hospital for three weeks history of blood streak sputum. There was no associated fever, night sweating, weight loss or contact history of tuberculosis (TB). He was an ex-smoker and social drinker. His body temperature was 37oC. Physical examination of the respiratory and cardiovascular system was normal. There was no finger clubbing or palpable cervical lymphadenopathy. Baseline blood tests, including complete blood picture, liver and renal function tests and clotting profile were normal. The erythrocyte sedimentation rate (ESR) was 60. Chest radiograph (Fig 1) on admission showed right apical haziness without cavitation. Sputum culture grew Klebsiella pneumoniae. While sputum for acid-fast bacilli (AFB) smear and cytology examination were negative.

Fig.1 CXR on admission: right apical hazziness

He was treated with amoxicillin and clavulanic acid initially, however, the blood streak sputum persisted. Therefore fibre-optic bronchoscopy was performed and revealed multiple nodules over the trachea down to the carina. There were also multiple patches of whitish material over the right main bronchus to right bronchus intermedius and left main bronchus. The right upper lobe was mildly blood stained. No active bleeding was identified. Transbronchial biopsy over right upper lobe showed acute on chronic inflammation suggestive of organizing pneumonia, and bronchial biopsy of the whitish material showed chronic inflammation only. The biopsy of tracheal nodule was attempted but failed due to its hard nature. The bronchial aspirate grew Pseudomonas aeruginosa, while AFB smear and cytology were negative. The antibiotic was then changed to ceftaxzidime and his blood streak sputum stopped.

Computed tomography (CT) of thorax (Figure 2a) showed 1.2cm air-filled cavitary lesion with associated band shadow and fibrosis at right upper lobe, this was suspicious of chronic old TB changes. There were nodularities over the trachea and bilateral main

21

bronchi (Figure 2b). CT neck and trachea (Figure 2c) with sagittal and coronal reformation was subsequently performed to delineate the tracheal lesion. It showed irregular calcified nodular protrusions from submucosal layer into the tracheal lumen which involved the anterior and lateral portions of the tracheal wall while spared the posterior membranous portion. It extended from thyroid cartilage to the trachea bifurcation. There was no tracheal stenosis.

Figure 2a. CT thorax: right upper lobe lesion Figure 2b. CT thorax: tracheal nodules

Figure 2c. CT trachea (sagittal): submucosal calcification of the tracheal nodule

The lung function test (Figure 3) was normal and there was no large airway obstruction by flow-volume loop.

Figure 3. Lung function test

The patient was subsequently referred to cardiothoracic surgeon for assessment of the right apical lesion and tracheal nodules. Bronchoscopic tracheal nodule biopsy was done and histology (Fig. 4) showed benign respiratory and squamous mucosa with fragments of

22

lamellar bone in the submucosa. While right video-assisted thoracoscopic wedge excision of right apical lesion showed fibrosis only and no malignancy. The bronchoscopic, radiological and histological diagnosis of the tracheal nodules was tracheobronchopathia osteochondroplastica.

Figure 4. Tracheal nodule biopsy. Hematoxylin and eosin x 100. Section shows bony fragments with marrow cavity closely applied to the subepithelial fibrous tissue.

Literature review Tracheobronchopathia osteochrondroplastica (TO) has two synonyms: tracheopathia chrondroosteoplastica, tracheopathia osteoplastica. It was first described in 1857 by Wilks at the autopsy finding of a 38 year old man died of pulmonary TB with the title “Ossific deposit on the larynx, trachea and bronchi”. In 1863, Virchow described the lesion as ecchondrosis and exostosis arising from the normal tracheal ring. Until 1910, Aschoff concluded it is the disorder of the connective tissue which specifically affecting the internal elastic membrane of the trachea and major bronchi and firstly named it tracheopathia osteoplastica.1

TO is a rare benign disorder usually find during autopsy in the past and by bronchoscopy or CT imaging nowadays. The incidence was reported to be 1:400 to 3:1000 in autopsy, and 1:125 to 1:6000 in in-vivo bronchoscopy. At Mayo Clinic, it has been 1:772 bronchoscopies.2 The etiology of TO is unknown although there had been reported association with ozena (atrophic rhinitis with thick mucopurulent discharge, mucosal crusting and fetor), silicosis, amyloidosis, and mycobacterial infection.3 There was no increased risk of malignancy and not related to smoking. In a retrospective study, Leske1 found 12% of the patients with TO were asymptomatic. While cough (54%) and sputum production (34%) were the most common respiratory symptom. Other symptoms included haemoptysis, dyspnoea, fever and dysphonia. Difficult intubation due to tracheal narrowing 4 or simulating asthma with wheezing 5 had been reported as the initial presentation. TO can be diagnosed by bronchoscopy or thoracic imaging. Bronchoscopy allows direct visualization of the multiple nodules which are often difficult to be biopsied due to its hardness. They are arising from the submucosa and protruding into the lumen of tracheobronchial tree, spreading over the anterior and lateral walls of the airways but sparing the posterior wall. The most common sites being upper (76%) and middle (78%) trachea and much less frequent when down to lobar (18%) or segmental (17%) bronchi.1 In CT thorax, TO appears as dense submucosal or protruded nodule with preference in anterior trachea and main bronchi. Submucosal calcification (61%) is common while tracheal stenosis is not frequent (10%).1 The histological examination of TO is characteristic with the presence of cartilage and bone in the bronchial submucosa. Although the nodules are present in the major airway, the lung function test of patient with TO are usually normal. In a small study with only 7 subjects, Tukiainen 6 found one

23

patient with reversible airflow obstruction and two with reduced FEV1. The mean follow up lung function test in 4.2 years showed no spirometric parameter deterioration. This was echoed by Leske 1 that 43% of the TO patients had normal spirometry and 17% with obstructive pattern were attributed to TO. The follow up spirometry in 5 years (+/- 3 years) of some of those patients showed no deterioration in FEV1, FVC and FEV1/FVC. The appearance of TO is drastic but it usually does not impose major problem to the patient. There is no specific treatment for TO apart from adequate humidification, avoid irritation and antibiotic therapy if infection occurs.

References 1. Leske V, Lazor R, Coetmeur D et al. Tracheobronchopathia osteochondroplastica. A study of 41 patients. Medicine.

2001;80: 378-390. 2. Prakash UBS. Tracheobronchopathia osteochondroplastica. Seminars in Respiratory and Critical Care Medicine 2002;

23: 167-175. 3. Baugnes PE and Delaunois LM. Mycobacterium avium-intracellulare associated with tracheobronchopathia

osteochondroplastica. Eur Resp J 1995; 8:180-182. 4. Coetmeur D, Bovyn G, Leroux P et al. Tracheobronchopathia osteochondroplastica presenting at the time of a difficult

intubation. Resp Med. 1997;91:496-498. 5. Park SS, Shin DH, Lee DH et al. Tracheopathia osteoplastica simulating asthmatic symptoms. Diagnosis by

bronchoscopy and computerized tomography. Respiration. 1995;62):43-435. 6. Tukiainen H, Torkko M, Terho EO. Lung function in patients with tracheobronchopathia osteochondroplastica. Eur

Resp J. 1988;1:632-635.

24

issertation Abstract

Heightened sympathetic activity in obstructive sleep apnoea Heightened sympathetic activity in obstructive sleep apnoea Heightened sympathetic activity in obstructive sleep apnoea Heightened sympathetic activity in obstructive sleep apnoea syndrome and its relationship to cardiovascular disease syndrome and its relationship to cardiovascular disease syndrome and its relationship to cardiovascular disease syndrome and its relationship to cardiovascular disease Dr. Chung-yan Chan Department of Medicine, North District Hospital

Background and methods Patients with obstructive sleep apnea syndrome (OSAS) were found to have high sympathetic activity. The effect of short-term nasal continuous positive airway pressure (nCPAP) on sympathetic activity among OSAS patients was evaluated in this study. Results Twenty-four hour urine catecholamine excretion in 26 newly diagnosed OSAS patient was measured before and after treatment with nCPAP for at least one month period. The results of 21 patients who completed two sets of 24-hour urine catecholamine measurements were analyzed. There was significant reduction in 24-hour urine nor-epinephrine excretion after nCPAP therapy, mean urine nor-adrenaline reduced from 376.9 to 285.0nmol/day, with a mean reduction of 91.86nmol/dL (SD 194.86, 95% CI 3.15 – 180.55, p = 0.043) Conclusion nCPAP therapy could effectively reduce sympathetic activity in patients with moderate to severe OSAS. The effect of nCPAP was evident even after a short period of treatment.

25

issertation Abstract

AAAA clinical review on management of epyemaclinical review on management of epyemaclinical review on management of epyemaclinical review on management of epyema thoracisthoracisthoracisthoracis//// complicated parapneumonic effusions in Kwong Wah Hospitalcomplicated parapneumonic effusions in Kwong Wah Hospitalcomplicated parapneumonic effusions in Kwong Wah Hospitalcomplicated parapneumonic effusions in Kwong Wah Hospital Dr. Wai Chen Department of Medicine and Geriatrics, Kwong Wah Hospital

Study objectives

To evaluate the treatment outcome of patients with complicated parapneumoic effusion (CPE) and empyema thoracis and to identify factors affecting the clinical response to antibiotics and drainage therapy.

Methods

Retrospective analysis of patient database from January 2001 to December, 2004 with a diagnosis of complicated para-pneumonic effusion or empyema thoracis in Kwong Wah Hospital were performed. Clinical data including age, sex, symptoms, biochemical and microbiological results, findings of chest imaging, drainage procedures, surgical intervention and survival outcome were collected. Comparison was made between the group of patients that was treated successfully with antibiotics plus intercostal pleural drainage versus the group that failed such treatment.

Results Fifty-eight patients were included in the analysis, with 48 patients (Medical Success group, 82.8%) successfully treated with antibiotics and/or intercostal drainage. The remaning 10 patients (Medical Failure group, 17.2%) did not respond to antibiotics and drainage so either surgery or death was resulted. Initial presentation with cough and sputum (N = 31 [65%] vs. N = 3 [30%], p = 0.044) and adequate ultrasound guided drainage (N = 36 [75%] vs. N = 3 [30%], p = 0.049) were significantly more common in the Medical Success group. Positive pleural fluid culture (N = 20 [42%] vs. N = 9 [90%], p = 0.001) and positive blood culture (N = 6 [13%] vs. N = 4 [40%], p = 0.045) were more commonly found in the Medical Failure group. In Multivariate analysis, positive pleural fluid culture was the only independent negative prognostic factor (p = 0.026) predicting medical treatment failure.

Conclusion

Positive pleural fluid culture was the most important poor prognostic indicator of complicated parapneumonic effusion and empyema thoracis. Early surgical intervention should be considered in this subgroup of patients who failed initial response to antibiotics & drainage therapy.

26

issertation Abstract

A prospective study on patients admitted with acute A prospective study on patients admitted with acute A prospective study on patients admitted with acute A prospective study on patients admitted with acute exacerbation of chronic obstructive pulmonary exacerbation of chronic obstructive pulmonary exacerbation of chronic obstructive pulmonary exacerbation of chronic obstructive pulmonary disease: clinical disease: clinical disease: clinical disease: clinical features, infectious aetiology and short term outcomefeatures, infectious aetiology and short term outcomefeatures, infectious aetiology and short term outcomefeatures, infectious aetiology and short term outcome Dr. Joan PC Fok Department of Medicine and Therapeutics, Prince of Wales Hospital Introduction Chronic obstructive pulmonary disease (COPD) is now estimated to be the fourth leading cause of death in Hong Kong. Patients with acute exacerbations of COPD (AECOPD) account for 3% of all hospital admissions. Not only does AECOPD cause significant decline in lung function, it also has the potential to jeopardize the quality of life of patients. The aim of this study was to assess the infectious aetiology, clinical features and short term outcome of patients admitted to hospital with AECOPD in Hong Kong. Methods This is a single-centre prospective study conducted at a tertiary teaching hospital in the Eastern New Territories region of Hong Kong. Patients admitted to the hospital with AECOPD from May to October 2004 were recruited. The symptoms, demographic data, co- morbidities, results of blood tests, sputum cultures, rapid tests and viral isolations on nasopharyngeal aspirates (NPA), antibiotic treatment and the length of hospital stay were noted. All recruited patients were subsequently reassessed in one month after their admissions with spirometry, weight and height measurements. All patients were then prospectively followed for a period of up to three months post admission. Clinical outcome such as readmissions and death was recorded. Results Altogether 178 patients were recruited and this corresponded to 257 episodes of AECOPD. The mean age (SD) of the patients was 76.3 (7.6) years. The mean FEV1 (SD) was 42.9 % (17.6) of the predicted values and the duration of hospital stay was 14.6 (14.8) days (median 11 days). Out of 257 episodes of AECOPD, of which one routine sputum culture was requested in each admission, 206 sputum samples were sent for routine bacterial culture within 48 hours after admission, and 53 (25.7%) had positive growth. Pseudomonas aeruginosa (6.8%), Haemophilus influenzae (6.3%) and Streptococcus pneumoniae (4.9%) were the commonest bacteria found in sputum cultures. 205 sputum samples were sent for mycobacterium culture and positive growth of mycobacteria was found in 6 (2.9%) whereas Mycobacterium tuberculosis was isolated in 3 sputum samples. In addition, 213 NPAs were sent for viral screening. 23 (10.8%) were subsequently found to be positive on viral culture. Influenza A was the commonest virus found with a prevalence of 7.5%. The mean and median lengths of stay of patients admitted with AECOPD were 14.6 (14.8) and 11 days respectively. The use of LTOT and NIPPV during admission were associated with a prolonged length of stay. 1 (0.4 %) episode of AECOPD required intubation whereas 41 (16 % of all episodes of AECOPD) received NIPPV. 57 (32%) patients were readmitted in 3 months. Patients on LTOT and those who were on inhaled corticosteroid were more likely to be readmitted. 17 (9.6%) patients died within 3 months after the index admission.

27

Conclusion In this group of elderly patients who were admitted with AECOPD between May and October 2004, 25.7% of the sputum cultures yielded positive growth of bacterial organisms, whereas 10.8% of the NPAs were positive for viral pathogens. These results suggest that bacterial and viral infections are important causes of AECOPD in our locality.

28

issertation Abstract

Management and outcome of empyema thoracis: experience in Management and outcome of empyema thoracis: experience in Management and outcome of empyema thoracis: experience in Management and outcome of empyema thoracis: experience in a regional hospital a regional hospital a regional hospital a regional hospital Dr. Wai-lam Law Department of Medicine, Queen Elizabeth Hospital

Introduction and methods This is a retrospective study to evaluate the clinical features, microbiological patterns, radiological features, management and outcome of patients with empyema thoracis in Queen Elizabeth Hospital. Results 53 eligible patients with empyema thoracis were included from 1st January 1999 to 31st December 2003. The most common presenting symptoms were fever (69.8%) and chest pain (64.2%). A significant proportion of our patients (41.5%) had known risk factors for developing empyema. The most common co-morbidities were diabetes mellitus (23.3%), previous cerebrovascular accident (11.6%) and carcinoma of lung (11.6%). Streptococcus milleri was the most common etiological agent. Loculations and pleural thickening were found in 58.5% and 49.1% of cases respectively. Image-guided catheter drainage was performed in 26 (49.1%) patients and the corresponding success rate was 57.7%, which was higher than that of conventional chest drainage (37%). A total of twenty patients (37.7%) were successfully treated with non-surgical method (antibiotics plus medical drainage) while 29 (54.7%) patients need surgical decortications. The mean hospital stay was 25.7 +/- 11.7 days. Prolonged hospitalization (greater than or equal to 30 days) occurred in 20 (37.7%) patients. Thirteen patients (24.5%) had adverse outcomes including intensive care utilization and death, with overall in-hospital mortality was 7.5% (4 cases died). Multivariate analysis showed that positive pleural fluid Gram’s staining for bacteria and presence of loculations on imaging were two independent predicting factors for non-surgical treatment failure in empyema thoracis. Conclusion Early aggressive surgical intervention should be considered in patients with loculated empyema or empyema with positive pleural fluid Gram’s staining for bacteria.

29

issertation Abstract

Clinical audit of longClinical audit of longClinical audit of longClinical audit of long----term oxygen therapy service in Ruttonjee term oxygen therapy service in Ruttonjee term oxygen therapy service in Ruttonjee term oxygen therapy service in Ruttonjee HospitalHospitalHospitalHospital Dr. Kwok-cheung Lung Department of Medicine, Ruttonjee Hospital

Background Oxygen is an effective drug used to treat various lung diseases and conditions associated with hypoxaemia or tissue hypoxia. Two previous randomized controlled trials (RCT) demonstrated that the administration of LTOT improved survival in selected patients with hypoxic COPD and possibly other hypoxic chronic lung diseases. Approximately 3600 patients were using long-term oxygen therapy (LTOT) in 2002, with an annual expenditure of more than $43 millions in Hong Kong, Aims The aim of this clinical audit was undertaken to investigate the use of LTOT for COPD patients in Ruttonjee Hospital (RH), to assess the adherence to MRC guidelines in prescription of LTOT, patient’s compliance with the medical prescription and survival of the patients. Methods A list of patients was generated from records from Oxygen Nurse in Ruttonjee Hospital. Data from these records was analysed including the demographic data. Data concerning the adherence to MRC prescription guidelines, compliance to prescription and Survival of patients using LTOT was only limited to those patients with LTOT prescribed in RH and follow up in RH Chest Special Out-patient Department. Results A total of 1245 patients referring LTOT in this hospital, 890 (71.5%) patients with LTOT started in RH, and 10.5 % of them were old cases of LTOT. Hypoxic COPD was the indication of LTOT in 903 (78.9%) of 1144 patients, 241 (21.1%) patients had other hypoxic lung diseases; 611 of 903 (67.7%) COPD patients had coexisting diseases including other lung diseases; only 291 (32%) of 903 patients had isolated COPD; the majority (88.3%) of the COPD patients had poor lung function. 580 of 890 (65%) patients with new LTOT installation treated and follow up in Ruttonjee Hospital, 458 of them had hypoxic COPD and included into compliance, adverse effects and survival analysis More than 80% of patients (in both hypoxic COPD and other hypoxic lung diseases) were indicated for LTOT and fulfilled the prescription guideline. Conclusion LTOT has been indicated for a number of hypoxic lung diseases, the most common one is hypoxic COPD; the adherence to prescription guideline was 86% in hypoxic COPD patients and 81% in other hypoxic lung diseases; Patents compliance to prescription was for COPD patients and overall crude survival rate for the COPD patients using LTOT in RH was 78.1%, 55.6%, 33.1%, 20.5%, 11.8%, 8.6% at 1, 2, 3, 4, 5 and > 5 years.

30

issertation Abstract

A study on haemoptysis on patients with bronchiectasis A study on haemoptysis on patients with bronchiectasis A study on haemoptysis on patients with bronchiectasis A study on haemoptysis on patients with bronchiectasis Dr. Clara SW Yan Tuberculosis and Chest Unit, Grantham Hospital Study objective Haemoptysis is an important and alarming symptom commonly found in patients with bronchiectasis. However it does not occur invariably in all patients with the disease. The relationships between haemoptysis with clinical, physiological, radiological and bacteriological parameters have not been systematically studied previously. This study is designed to characterize the clinical, physiological, radiological and microbiological profiles of bronchiectasis patients and to evaluate these parameters with respect to the occurrence of haemoptysis. Design Cross-sectional prospective evaluation Methods Patients with proven bronchiectasis by high resolution computed tomography (HRCT) at their steady state were recruited from a specialist respiratory clinic. Various parameters including the aetiology, clinical features, radiology, physiological function and microbiological characteristics were evaluated. These results were further analyzed by comparing patients with and without experience of haemoptysis. Results 129 patients with bronchiectasis were evaluated. They were predominantly female with onset of symptoms at their forties. 72% of them were idiopathic. The most commonly reported symptoms, in descending order, were cough, fatigue, exercise intolerance, wheeze and haemoptysis. Haemoptysis occurred in 38% of the patients. In comparing patients with and without haemoptysis, those in the haemoptysis group had significantly better lung function indices including the forced expiratory flow in one second (FEV1) and forced vital capacity (FVC), with a difference of 300ml and 400ml respectively. History of smoking appeared to be related to the occurrence of haemoptysis, although not statistically significant (p=0.053). No statistically significant difference was observed in relation to a history of tuberculosis with haemoptysis. Fatigue and reduction in exercise intolerance were less common among patients with haemoptysis, though not statistically significant (p=0.065 and 0.061 respectively). Right lower lobe involvement had a significant effect to the prediction of the status of haemoptysis by logistical regression (p=0.01). Right lung involvement was also significant in predicting the occurrence of haemoptysis (p=0.049). There was no difference in the sputum characteristics, microbiology, exacerbation and quality of life (St George’s Respiratory Questionnaire) when comparing patients with and without haemoptysis. There were 75 patients who could recall the number of haemoptysis episodes in the past 12 months. Of these, 26 had at least one episode (mean 1.52 ±3.78) in the past 12 months. The duration, measured as the number of days, for each time was 2.46 ±2.44. Thirteen out of 26 patients had fresh haemoptysis but produced only small amount of sputum (84.6% produced less than 20ml/day). Sputum production of more than 5ml daily was significantly related to the occurrence of haemoptysis (p=0.04).

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Conclusion Haemoptysis occurs in 38% of patients. Better lung function is observed in the group of patients with haemoptysis than their counterparts. They are more likely to be non-smokers. Right lower lobe involvement is found to have a significant effect and right lung involvement is slightly significant to the occurrence of haemoptysis. The two groups do not differ in sputum characteristics, pathogens identified in sputum, quality of life and exacerbation frequency. For fresh haemoptysis, daily sputum production of more than 5ml is significantly related to the occurrence of haemoptysis.

32

issertation Abstract

Clinical chaClinical chaClinical chaClinical characteristics, treatment modalities and outcomes of racteristics, treatment modalities and outcomes of racteristics, treatment modalities and outcomes of racteristics, treatment modalities and outcomes of spontspontspontspontaneous pneumothorax in a regional hospitalaneous pneumothorax in a regional hospitalaneous pneumothorax in a regional hospitalaneous pneumothorax in a regional hospital Dr. Betty H.K. Young Respiratory Medical Department, Kowloon Hospital

Objectives The aims of this study were to identify the clinical characteristics of patients with spontaneous pneumothorax (SP), to compare the treatment modalities with published guidelines, to analyse the outcomes and to identify the risk factors associated with recurrence of SP. Methods A retrospective study on patients admitted for SP via Accident and Emergency Department in a general hospital in the period from January 2002 to December 2002. Results A total of 101 patients included 54 primary spontaneous pneumothorax (PSP) and 47 secondary spontaneous pneumothorax (SSP) were identified. Younger patients were usually presented with PSP and older patients with SSP. Male predominance was observed in both groups. Compared with PSP patients, more SSP patients had statistically significant history of smoking, symptom of dyspnoea, and underlying chronic obstructive pulmonary disease (p<0.05). Sixty-eight (67.3%) patients were inserted with large-bore chest drain as initial treatment of SP. Patients treated with chest drain had a better immediate success rate than those treated with manual aspiration (p<0.05), while the former group of patients had a higher success rate during hospitalization than both the conservative treatment group and the aspiration group (p<0.05). Older patients and more ex-smokers had undergone chemical pleurodesis than surgery (p<0.05), but more PSP patients had surgical treatment performed than SSP patients (p<0.05). Compared with the chemical pleurodesis group, the recurrence rate in 2 years in the surgical treated group was statistically lower and there were no differences in their complications and mortality (p<0.05). Chronic obstructive pulmonary disease was the only factor which significantly associated with the recurrence of pneumothorax. Conclusions This study describes the clinical characteristics of SP and its treatment variations among doctors in hospital. Large-bore chest drain insertion for the initial treatment of SP remains the most popular method. The presence of chronic obstructive pulmonary disease is a major predictor in recurrence rates and therefore more aggressive preventive intervention should be considered for all these group of patients.

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ractical Corner

This section serves to bombard the trainees with questions covering the basic concepts in respiratory medicine. Questions asked will be discussed in the next issue. Specialists and trainers are invited to give their brief discussions. In no way is it meant to be exhaustive or comprehensive, it only serves to highlight important concepts. Specialists are welcome to offer questions (and the discussions) for this section. Trainees are also welcome to give comments, particularly when there is query on what had been published. Please send them to the editor email: fannyko@cuhk.edu.hk Questions for the next issue:

1. What are the limitations of pulse oximetry? (from Dr. Wilson KS Yee, Kwong Wah Hospital)

2. How can nylon flock and microwave-popcorn affect our lung? (from Dr. WS Leung, United Christian Hospital)

3. Bronchodilators delivery by pressured metered dose inhaler (pMDI) with spacers or nebulizer in acute airway diseases in adult. How comparable are they?

(from Dr. CK Ng, Queen Elizabeth Hospital)

34

ractical Corner

What are the ways to diagnose latent tuberculous infection? What are the ways to diagnose latent tuberculous infection? What are the ways to diagnose latent tuberculous infection? What are the ways to diagnose latent tuberculous infection? Dr. Wai- kei Lam Department of Medicine, North District Hospital

The classical way is by the tuberculin test. Tuberculin (purified protein derivative (PPD)) is used as an antigen to elicit a delayed type IV cellular hypersensitivity response in the form of skin induration when it is injected intradermally. The response is measured as the transverse diameter of induration in millimeters at 48-72 hours. Presence or absence of latent tuberculosis infection is dichotomized by a cut-off size that is set according to the subject’s pre-test probability of latent tuberculosis infection. The test, though regarded as “gold standard” in diagnosis of (and albeit the only way in the past to diagnose) latent tuberculosis, can be non-specific. This is because PPD is a heterogenous mixture of antigens, many of which are shared among Mycobactrium tuberculosis, M. bovis bacille-Calmette-Guérin (BCG) and certain nontuberculous mycobacteria. Sensitivity can also be low in immunosupressed or anergic patients.1, 2

Immunodiagnosis is a recent advance in diagnosis of latent tuberculosis. The technique is made possible with the advent of molecular biology and identification of M. tuberculosis specific antigens. Early secretary antigenic target 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) are two low molecular weight proteins encode by genes located within the region of difference 1 (RD1) segment of the M. tuberculosis genome. ESAT-6 and CFP-10 are considered specific for the M. tuberculosis complex as the antigens are absent in all BCG substrains and most other nontuberculous mycobacteria (except M. kansasii, M. marinum and M. szulgai).3,4

Leucocytes in peripheral blood sample are allowed to come in contact with reagents containing ESAT-6 and CFP-10. When there is ongoing (latent) mycobacterial infection, effecter T cells in the subject’s peripheral blood become sensitized to ESAT-6 and CFP-10 and will produce γ-interferon upon re-encounter of the antigens in vitro. The magnitude of response is determined either by measuring the concentration of γ-interferon in serum by enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold/ QuntiFERON-TB Gold In-tube, Cellestis, Australia), or by counting the number of mononuclear cells expressing γ-interferon using the enzyme-linked immunosorbent spot (ELISPOT) technique (T-SPOT.TB, Oxford Immunotec, UK). Both methods require incubation of blood or harvested peripheral blood mononuclear cells with the antigens for 16-24 hours.5,6 Prolonged incubation is deliberately not performed as this will in addition recruit the response of memory T cells, which produce γ-interferon even if the subject has no latent but just old and cured M. tuberculosis infection.7 Early generation of the assay had used PPD as the antigen to elicit γ-interferon response (QuantiFERON-TB).8 Commercial assays currently available use RD1-based antigens to obtain high specificity and a cocktail (ESAT-6 admixed with CFP-10) instead of single antigen to enhance test sensitivity.9

Theoretical advantages of the technique, when compared to the tuberculin test, include a more objective measurement method, no need for a second visit, increased specificity in BCG-vaccinated subjects, and unchanged result on repeat testing (tuberculin skin test has boosting phenomenon).1

Studies have investigated clinical performance of immunodiagnostic methods when compared to the tuberculin skin test. Major difficulty in assessing test sensitivity is the lack of a true gold standard for diagnosis of latent mycobacterial infection. Investigators have therefore used quantified degree of exposure to patient with

35

pulmonary tuberculosis (e.g. proximity and duration of contact with the index case in outbreaks or household contacts) as a surrogate for risk of latent tuberculosis infection. In such settings RD1-antigen based assays have a significantly higher odds ratio (an estimate of test sensitivity) or correlation with degree of exposure when compared to tuberculin skin test, using 5-10 mm as cut-off for a positive test.10, 11, 12,

13 Specificity can be determined by testing subjects from a low prevalence population. The specificity of RD1-based tests are the same/similar as tuberculin skin test before (100% vs. 100%) and after (100% vs. 98%) BCG-vaccination in one study. 14 In another study the assay specificity is better than tuberculin skin test in BCG-vaccinated subjects (98% vs. 68%). Both studies used 15 mm as cut-off for a positive tuberculin test. 15

As the number of mononuclear cells tested are kept constant (250,000 cells per microtitre plate well), immunodiagnosis by the ELISPOT technique may maintain its sensitivity even in anergic or immunosupressed subjects.6 It has in fact demonstrated high sensitivity in HIV-infected subjects with active tuberculosis.16 Whether ELISPOT-based method is superior to tuberculin skin test in diagnosis of latent tuberculosis in immunocompromised patients and whether it is better than the ELISA-based method warrants further studies. Immunodiagnosis of latent tuberculosis will be of great value if it can be proved that the assays are more sensitive in patients with rheumatoid arthritis, where tuberculin test has low sensitivity and the use of anti-TNF alpha therapy requires exclusion of latent tuberculosis infection.17-18 Both T-SPOT.TB and QuantiFERON-TB Gold assay are approved by the European Union and QuantiFERON-TB Gold assay is approved by the US Food and Drug Administration.5.6 Nevertheless, these tests have not been studied extensively in endemic countries with high prevalence of latent tuberculosis and BCG coverage.9 Such trials shall provide scientific basis for the use of these tests in a larger scale in our locality. Longitudinal studies have demonstrated that treatment of latent tuberculosis diagnosed by tuberculin skin test results in reduced cases of active tuberculosis.19 Further trials are therefore required to address the question of ultimate concern - whether treating latent tuberculosis diagnosed by immunodiagnostic techniques can result in a fewer number of active tuberculosis cases when compared to strategy using tuberculin skin test.

Reference: 1. American Thoracic Society, Centers for Disease Control and Prevention. Diagnostic standards and classification of

tuberculosis in adults and children. Am J Respir Crit Care Med 2000;161:1376-1395. 2. Lee E, Holzman RS. Evolution and current use of the tuberculin test. Clin Infect Dis 2002;34:365-370. 3. Andersen P, Munk ME, Pollock JM et al. Specific immune-based diagnosis of tuberculosis. Lancet 2000;

356:1099-1104. 4. Arend SM, van Meijgaarden KE, de Boer K et al. Tuberculin skin testing and in vitro T cell responses to ESAT-6

and culture filtrate protein 10 after infection with Mycobacterium marinum or M. kansasii. J Infect Dis 2002; 186:1797-1807.

5. Cellestis Ltd. QuantiFERON®-TB Gold Technical Information. Available at: http://www.cellestis.com. Accessed October 10, 2005.

6. Oxford Immunotech Ltd. How T-SPOT™.TB works. Available at: http://www.oxfordimmunotec.com. Accessed October 10, 2005.

7. Dheda K, Udwadia ZF, Huggett JF et al. Utility of antigen specific interferon-gamma assay for the management of tuberculosis. Curr Opin Pulm Med 2005; 11:195-202.

8. Mazurek GH, Villarino ME. Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention. MMWR Recomm Rep 2003; 52:15-18

9. Pai M, Riley LW, Colford JM Jr. Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect Dis 2004; 4:761-776.

10. Lalvani A, Pathan AA, Durkan H et al. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001; 357:2017-2021.

11. Ewer K, Deeks J, Alvarez L et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet 2003; 361:1168-1173.

12. Brock I, Weldingh K, Lillebaek T et al. Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. Am J Respir Crit Care Med 2004; 170:65-69.

13. Richeldi L, Ewer K, Losi M et al. T cell-based tracking of multidrug resistant tuberculosis infection after brief exposure. Am J Respir Crit Care Med 2004; 170:288-295.

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14. Johnson PD, Stuart RL, Grayson ML et al. Tuberculin-purified protein derivative-, MPT-64-, and ESAT-6-stimulated gamma interferon responses in medical students before and after Mycobacterium bovis BCG vaccination and in patients with tuberculosis. Clin Diagn Lab Immunol 1999; 6:934-937.

15. Mori T, Sakatani M, Yamagishi F et al. Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 2004; 170:59-64.

16. Chapman AL, Munkanta M, Wilkinson KA et al. Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells. AIDS 2002; 16:2285-2293.

17. Ponce de León D, Acevedo-Vásquez E, Sánchez-Torres A, et al. Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis. Ann Rheum Dis 2005; 64:1360-1361.

18. British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment. Thorax 2005; 60:800-805.

19. American Thoracic Society, Center for Disease Prevention and Control. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161:S221-S247.

37

ractical Corner

How do you work up a patient with suspected idiopathic How do you work up a patient with suspected idiopathic How do you work up a patient with suspected idiopathic How do you work up a patient with suspected idiopathic interstitial pneumoniainterstitial pneumoniainterstitial pneumoniainterstitial pneumonia???? Dr. KC Wong Respiratory Medical Department, Kowloon Hospital Some interesting areas regarding the investigations of patients with suspected idiopathic interstitial pneumonia (IIP) would be discussed in this article.

The role of high resolution computerized tomography (HRCT) HRCT is indicated for almost all suspected idiopathic interstitial pneumonia (IIP). The primary role of HRCT is to separate patients with typical findings of idiopathic pulmonary fibrosis (IPF)/ usual interstitial pneumonia (UIP) from those with the less specific findings associated with other IIP.1 A confident radiological diagnosis of UIP on HRCT can be made from a bilateral, predominantly basal and subpleural reticular pattern, associated with subpleural cysts (honeycombing) with or without traction bronchiectasis. It is correct in more than 90% of cases.2,3 The role of bronchoscopy Transbronchial biopsies are not generally considered to be useful in the diagnosis of most IIP, with the exception of diffuse alveolar damage (DAD), acute interstitial pneumonia (AIP), and occasionally cryptogenic organizing pneumonia (COP/BOOP). The primary role of transbronchial biopsies is to exclude sarcoidosis and certain infections. Bronchoalveolar lavage is also not always helpful in the assessment of IIPs, except in rare conditions such as pulmonary alveolar proteinosis, where characteristic features might aid in the diagnosis.

The role of surgical lung biopsy Surgical lung biopsy provides a histological diagnosis, which allows a more definitive characterization of the various IIP entities than radiological imaging. A histological diagnosis provides the basis for clinico-radiologic-pathologic diagnosis.

In the absence of contraindications, surgical lung biopsy is advised in all patients with suspected IIP who do not show a typical clinical and HRCT picture of IPF/

UIP.1

The reasons are three-fold: First, IPF/UIP has a poor prognosis among the IIP, and is believed to be poorly responsive to the currently available therapy.4

Second, a definitive diagnosis of other forms of IIP can only be established with the aid of a surgical lung biopsy. Almost all of the current treatments for the IIP have potentially serious side effects, and it is thus unreasonable to expose patients to these risks in the presence of diagnostic uncertainty. Finally, in those patients without the stereotypical HRCT features of UIP, there is a significant difference in survival between those found to have histological non-specific interstitial pneumonia (NSIP) and those with histological UIP. Surgical lung biopsy is therefore required in these patients to provide accurate prognostic

information. Furthermore, among patients with a histological diagnosis of UIP, there is a difference in survival between those with HRCT features suggestive of UIP and those without such HRCT features.5

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Safety of surgical lung biopsy

The availability of minimal invasive technique in the form of video-assisted thoracoscopic lung biopsy has made it more acceptable for clinicians to recommend surgical lung biopsy to their patients with diffuse parenchymal lung diseases. In a study evaluating the outcomes and safety of surgical lung biopsy for interstitial lung disease7, the 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). The only predictors of perioperative mortality were either the need for mechanical ventilation at the time of surgical lung biopsy or the subjects were immunosuppressed prior to surgical lung biopsy. After excluding these 2 categories, an overall 90-day post-surgical lung biopsy mortality rate was 1.5%.

Communication with thoracic surgeons Efforts should be made to communicate with the thoracic surgeons. The communication should include the following issues: 1. The lung biopsy should ideally include the full spectrum of the gross appearance,

including the “honeycomb” foci, because these can confirm severe fibrosis, one of the criteria for UIP.

2. Surgical lung biopsies should be obtained from more than one lobe of the lung. HRCT scanning may guide the surgeon to the most optimal biopsy sites. In a study to explore the histological variability in surgical lung biopsy specimens from multiple lobes in patients with IIP 6, Flaherty et al. found different histological pattern (UIP and NSIP) between different lobes in 26% of the patients. They also showed that if UIP pattern was present in one of the lobes and NSIP pattern was present in one or more of the other lobes, the clinical behaviour was similar to that of UIP.

3. The surgeon must also attempt to avoid deflation of the specimen through clamping, as this complicates interpretation of histological findings. Specimen

atelectasis can be corrected by inflating the lung biopsies with formalin either by injection with a syringe or by gently shaking thin slices of the lung biopsy specimen in the specimen container before paraffin processing.8

Search for a specific etiology In clinical practice, patients are commonly having mis-classified IIP because of inadequate history taking. An increasing number of associations between the development of IIP, occupational, environmental, and drug exposures are being

described (Fig 1). It is thus important to re-evaluate the patient in a search for a specific etiology, particularly when NSIP, DAD, and lymphoid interstital pneumonia (LIP) are found on lung biopsy. For instance, NSIP pattern could be related to no detectable cause (idiopathic NSIP), collagen vascular disease, hypersensitivity pneumonitis, drug-induced pneumonitis, infections, and immunodeficiency including HIV infection.

Multi-disciplinary Approach It is recommended1 the final diagnosis should only be obtained after the clinical, radiological, and pathological data has been assessed by pulmonologists, radiologists, and pathologists.

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Figure 1. Clinicopathological entities of idiopathic interstitial pneumonia (Am J Respir Crit Care Med 2002;165,277-304.). References:

1. Joint Statement of the American Thoracic Society and the European Respiratory Society: American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165,277-304.

2. Hunninghake GW, Zimmerman MB, Schwartz DA, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001;164:193-196.

3. Raghu G, Mageto YN, Lockhart D, et al. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: a prospective study. Chest 1999;116:1168-1174

4. Collard HR, Ryu JH, Douglas WW et al. Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest 2004;125:2169 - 2174.

5. Flaherty KR, Thwaite EL, Kazerooni EA, et al Radiological versus histological diagnosis in UIP and NSIP: survival implications Thorax 2003;58:143-148.

6. Flaherty KR, Travis WD, Colby TV et al. Histopathologic Variability in usual and nonspecific interstitial pneumonias Am J Respir Crit Care Med. 2001;164: 1722-1727.

7. Lettieri CJ, Veerappan GR, Helman DL et al. Outcomes and safety of surgical lung biopsy for interstitial lung disease Chest 2005;127:1600-1605.

8. Churg A. An inflation procedure for open lung biopsies. Am J Surg Pathol 1983;7:69-71.

40

ractical Corner

What What What What physical and aerodynamic properties of radon in making it physical and aerodynamic properties of radon in making it physical and aerodynamic properties of radon in making it physical and aerodynamic properties of radon in making it an important etiology of lung cancer? an important etiology of lung cancer? an important etiology of lung cancer? an important etiology of lung cancer? Dr. Henry Kwok Department of Medicine, Ruttonjee Hospital

Radon is a radioactive noble gas which gives rise to progeny that are themselves radioactive. Some of these progenies have short half lives and undergo alpha decay, before these progenies deposit in the bronchial epithelium. Radon can exert its effects on the lungs by two means: either as free gas or as an attachment to surrounding air particles. As a free gas, radon tends to penetrate deeply into the lung periphery; however, if the radon is adsorbed to other particulate matters, the attached radon will then follow the distribution of the particulate matters dictated by their aerodynamic properties. It is also known that for particulate matters of the size range of 0.1-1µm, the time of suspension in the air tends to be the longest, and may last for days to weeks. For particles larger than 1µm, the air suspension time is much shorter (about 1 hour) due to the effect of gravity. Two factors have been noted to influence the deposition of particles in the lung: 1) the particle size and 2) the respiratory rate. Coarse particles (size>1µm) tend to deposit in the large airways, with some penetration into the smaller airways when the respiratory rate is slow. However, for smaller particles (size<1µm), the particles can penetrate to the periphery of the lung, and thus carry along the adsorbed matters, including radon. The radioactive decay of radon inside the airways will then be the crucial step in its carcinogenic potential. Alpha particles will be formed which will penetrate into the bronchial epithelium. Although alpha particles could only penetrate a very short distance (e.g. cannot even pass through a piece of paper), such alpha decay inside the bronchial tree will have a dramatic effect on the bronchial epithelium and thus carcinogenic potential. These aerodynamic properties can also explain the different degree of penetration of radon in the lungs between uranium mining exposures and household exposures. During uranium mining, certain level of physical exercise is present. The adsorbed radon will deposit predominantly in the larger airways and even the nostrils (if the very course particles are considered) due to the high respiratory rate. In contrast, in household exposure of radon, the relatively slower respiratory rate and finer particulate matters (compared to a uranium mine setting) will favour the distribution of radon to the more periphery of the lungs and therefore with different health effects.

Further Reading:

1. Krewski D, Lubin JH, Zielinski JM, et al. Residential radon and risk of lung cancer: a combined analysis of 7 North American case-control studies. Epidemiology. 2005 Mar;16(2):137-45.

2. Chen J. Estimated risks of radon-induced lung cancer for different exposure profiles based on the new EPA model. Health Phys. 2005;88:323-33.

41

edcial Statistics Corner

Medical Biostatistics Medical Biostatistics Medical Biostatistics Medical Biostatistics

Dr. Julie Wang University Department of Medicine, Queen Mary Hospital

Comparing the difference of variables between 2 or more populations : by using various statistical testings In previous sessions, we have discussed about normal and nonnormal distribution, and we also have some concepts of how to estimate a parameter.

This time, we are going to know more about statistical testings. Here, what we are dealing with is the entity “variation”. A random variable carries different values which constitute the variation, where the difference of each value from the centre point e.g. mean or difference of means, could be explained by chance alone. A parameter estimate has its own range of variability, as denoted by the standard error of means. Under such circumstances, how can we be sure whether the 2 different values of a parameter, derived from 2 samples of a population, could be explained by chance or not? Since we cannot eliminate variation, we have to take into account of its effect when we compare the variable between 2 samples of population.

The cornerstone of statistics is to answer the question of whether an observed difference of a parameter between 2 samples of population could well be explained by the variability of a parameter estimate, or if not, to what level of confidence is it due to a genuine difference in the 2 populations from which they are derived (Figure 1).

Figure 1. Do the means of the 2 samples of a population differ by chance, or are due to a real difference between the 2 populations from which they are derived?

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Let us go through the following questions before we conclude on the answer: 1. What are the principles of performing a statistical test? 2. What are the various types of statistical tests, and how to choose them appropriately 3. How to state and interpret the result of a test? 4. What is inference making , what are the possible errors?

1. What are the principles of performing a statistical test? Identify a parameter of interest

Look at the data distribution and nature; is it normal or nonnormal, paired or unpaired

Set a null H0 and an alternative HA hypothesis, determine one-sided or two-sided test nature

Choose an appropriate test: choose parametric or nonparametric test; paired or unpaired counterpart; note sample size effect

Interpreting the result: p-value or confidence interval

Making inference, consider errors

2. What are the various types of statistical tests, and how to choose them appropriately? Parametric tests are divided into procedures for discrete data and continuous data, which actually provide test statistics for standard error of means (eg z and student t test), proportions and variances (e.g. X2 test) etc ( Figure 2&3). Nonparametric tests provides test statistics for medians , difference of medians and arbituary ordinal ranking, e.g. Mann Whitney U test and Wilcoxon rank sum test etc. These tests have their paired and unpaired counterparts, to serve different data nature; and modified form for correction of small sample data.

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3. How to state and interpret the result of a test ? We state the result of a statistical test in terms of either a probability value, the p value; and or a confidence interval. p value indicates the probability of obtaining a result at least as extreme as that observed in a study by chance alone, assuming that the null hypothesis is true( i.e/ H0 is true). The smaller the p value, the lower the probability for the observed difference being due to chance alone, and the more evidence is it against H0. Confidence interval (CI)is a range of values, estimated to a certain level of precision on the basis of sample data, which is likely to cover the parameter of interest. For tests using standard errors of means, a CI which lies beyond zero is considered to be statistically significant enough to reject H0. On the other hand, if tests for proportions generate a CI lying outside of 1, then H0 could be rejected. Nowadays, CI is the more preferred form of presentation, as it provides information on the range of estimates, as well as the precision level , apart from only conveying the message of whether the test is statistically significant or not. Besides, the range of estimates gives us idea about whether the values are also clinically significant.

4. What is inference making, what are the possible errors ? Inference making is the process of decision making basing on test statistic result. Now that we have the p value, but how do we make a decision of whether to reject H0 or not ? We have to determine in advance a decision level α, which is the level of significance, where the decision is to reject H0 if p value < α, and vice verse .This level of significance is usually chosen at 0.05. Whatever the decision we make, there is always a chance of making an error. What matters is whether this chance is acceptably small or not (Figure 4). For instance, if a study of certain sample size shows that smoking is associated with lung cancer, where the p value for H0 is 0.04, and H0 is therefore rejected. We have to bear in mind that there is still a probability of 0.04 that H0 is true. This can also mean that if the same study is repeated 100 times, then there are about 4 episodes that the result will show evidence for the null hypothesis. However, these 4 episodes are considered to occur by chance, instead of the null hypothesis being the true association.

Figure 4. There are 4 possible outcomes for a statistical test

46

Type I error is the probability of rejecting H0 ( accepting HA) when in fact H0 is true. This equals α, and also refers to false positive.

Type II error is the probability of accepting H0, when in fact HA is true. This equals β, also refers to false negative (Figure 5).

Figure 5. Inference making and types of errors

References: 1. Brown L. Epidemiology in Medicine. Hennekens, Burring. 2. Altman, Machin , Bryant, Gardner. Statistics with Confidence. Second Edition. BMJ. 3. Moore D.S., McCabe GP. Introduction to the Practice of Statistics. Third Edition. Freeman. 4. Jekel JF, Elmore JG, Katz DL. Epidemiology Biostatistics and Preventive Medicine. W.B. Saunders.

Column

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Name of the book: High-resolution Computed Tomography of the Lungs: A Pattern Approach Publisher: Hodder Arnold 1st edition (August 2005) ISBN: 0-340-90580-8

D

ook Review Column

esigned for easy reference in the clinical setting, this is a comprehensive but practical guide to the interpretation of CT studies of

the chest. It also includes an appendix of useful information relating to chest imaging, including key facts about all the commonly encountered pathologic entities and protocols that can be referred to in the clinical setting. The book is accompanied by a CD containing all the images from the book with a presentation on pattern approach that can be used for teaching purposes as well as self-assessment.

Members of Hong Kong Thoracic Society will enjoy 10% discount

when ordering the book(s) under the “Book review column” through McBarron Book Co. 麥伯倫醫護圖書中心

Enquiry and Ordering Tel: (852) 2770 8521 Fax: (852) 2385 6236. (Free Delivery Service to local hospitals included)

Note: Book ordering will be dealt with directly by McBarron Book Co and the two Thoracic Societies are not responsible for any liabilities.

48

iary of International Conferences

29 October – 3 November, 2005 Montreal Canada

CHEST 2005 Info: www.chestnet.org/CHEST

11-14 November, 2005 Guangzhou China

10th Congress of the APSR 1st Joint Congress of the APSR/ACCP Info: www.apsr2005.com

E-mail: apsr2005@asia.cmpmedica.com

30 January – 1 February, 2006 New Orleans USA

42st Annual Meeting of The Society of Thoracic Surgeons Info: www.sts.org

Email: sts@sba.com

3-7 March, 2006 Miami Beach, USA

62st Annual AAAAI Meeting Info:http://www.aaaai.org/members/meetings/future_meetings.stm

24-29 March, 2006 Canberra Australia

TSANZ ASM Info: www.thoracic.org.au

1-3 June, 2006 Tokyo Japan

46th JRS Meeting Info: www.jrs.or.jp

19-24 May, 2006 San Diego USA

American Thoracic Society (ATS) International Conference Info: www.thoracic.org

2-6 September, 2006 Munich Denmark

16th ERS Annual Congress Info: http://www.messe-muenchen.de/ Email: newsline@messe-muenchen.de

2–6 September, 2007 Seoul Korea

The 12th World Conference on Lung Cancer – International Association for the Study of Lung Cancer (IASLC) Info: http://www.iaslc.org/ Email: WCLC2007@ncc.re.kr

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orthcoming Clinical Meetings

Date Hosting Hospital / Centre

November 6, 2005 Autumn Respiratory Seminar

Date Hosting Hospital / Centre

January 19 ,2006 Yan Chai Hospital and Hong Kong Lung Foundation Fellows

March 19, 2006 Annual Scientific Meeting

50

seful Websites

Medical Societies

Hong Kong Thoracic Society http://www.medicine.org.hk/hkts/home.htm

ACCP (HK & Macau Chapter) http://www.medicine.org.hk/accp/home.htm

American College of Chest Physician http://www.chestnet.org/

American Thoracic Society http://www.thoracic.org/

British Thoracic Society http://www.brit-thoracic.org.uk/

Canadian Lung Association http://www.lung.ca/

European Respiratory Society http://www.ersnet.org/

National Heart, Lung and Blood Institute http://www.nhlbi.nih.gov/

Society of Critical Care Medicine (USA) http://www.sccm.org/home/sccm_home_set.html

American Association for Respiratory Care http://www.aarc.org/index.html

The Federation of Medical Societies of HK http://www.medicine.org.hk/fmshk/

Publications

American Journal of Respiratory and Critical Care Medicine http://ajrccm.atsjournals.org/

American Journal of Respiratory Cell and Molecular Biology http://ajrcmb.atsjournals.org/

Asian Medical News http://www.amn.com/

British Medical Journal http://www.bmj.com/

Canadian Respiratory Journal http://webserver.pulsus.com/Respir/home.htm

Allergy, Asthma & Immunology Online http://allergy.mcg.edu

Chest http://www.chestjournal.org/

Current Opinion in Pulmonary Medicine http://www.currentopinion.com

Lancet Interactive http://www.thelancet.com/

Medscape respiratory care http://respiratorycare.medscape.com/home/ topics/respiratorycare/respiratorycare.html

Morbidity and Mortality Weekly Report http://www2.cdc.gov/mmwr/

New England Journal of Medicine http://www.nejm.org/content/index.asp

Postgraduate Medical Journal http://www.postgradmedj.com/

Respiratory Care Online http://www.rcjournal.com/

Thorax http://www.thoraxjnl.com/

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hest – Full Text On-Line

The Official Journal of ACCP is now on-line but is only available to subscribers (Fellows, members or affiliated members). Trainees are welcome to join at a very privilege rate (US30 per year). Applications should be directed to ACCP (USA) through their trainers (who must be a Fellow of the ACCP). Proof and detail of training (tentative period of training) is required. Any query can be directed to the Secretary, ACCP (HK and Macau Chapter) (see page 1). Browsing of information is available on the ACCP website: http://www.chestnet.org/membership/categories.html

embership News

♦ As of September 2005, there are 918 Members (233 Ordinary members, 6 Honorary members, 58 Life members and 621 Associate members).

♦ To be eligible for Life membership, 3 years of full membership

prior to the application is necessary. Please write to the Honorary Secretary (Dr W M Chan, Intensive Care Unit, Queen Mary Hospital, Pokfulam, Hong Kong) and send with a cheque of HK$2,000. Acceptance will be decided in the Hong Kong Thoracic Society council meeting.

♦ It is due to renew your membership, please fill in the

application/renewal form (available at http://www.fmshk.com. hk/hkts/member.htm) and send to Dr Loletta So (address as on the form) with the subscription (HK$100/200 for assoicate/ordinary members respectively), (cheque payable to HONG KONG THORACIC SOCIETY LTD). Members who had their names deleted should re-apply as new members. For enquiry, or checking your membership status, please reach Dr Loletta So by email (loletta.so@hotmail.com) or fax (852 2515 3182) (Please supply your name and fax number). Apology for not entertaining telephone enquiry.

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unds and Grants

Hong Kong Lung Foundation Fellowship

The fellowship is open to medical practitioners, allied health professionals, scientists, students and others for travelling aboard to engage in research, study and training in order to gain experience in modern methods of diagnosis, prevention and treatment of diseases of the respiratory system. Please note that priority will be given to active members of the Hong Kong Thoracic Society.

The Hong Kong Lung Foundation Fellowship has three types of Awards as specified below:

1. Open to members of the medical profession granting a sum up to HK$50,000 for training of 3 to 9 months and a sum up to HK$60,000 for training of over 9 months. 2. Open to members of the nursing/paramedical profession granting a sum up to HK$30,000. 3. Open to all members of the medical, nursing and paramedical profession granting a sum up to HK$30,000 for attending conference or short training course of 3 months or less.

Hong Kong Lung Foundation Fellowship which opens its application twice a year in June and December. Applicants should submit the application forms to the Hon Secretary of the Hong Kong Lung Foundation, not later than 30th June and 31st December of each year.

Application procedures and application form of Fellowship program can be downloaded from Hong Kong Lung Foundation Website: http://www.hklf.org/HKLF/hklf_fellows_e.htm

Hon secretary: Dr KS Chan, Pulmonary & Palliative Care Unit, Haven of Hope Hospital, Tseung Kwan O, Kowloon , Hong Kong. Fax: 2703 8799 Email: chanks@ha.org.hk

The Hong Kong Lung Foundation was established in 1996 to nurture advancement in clinical practice in the field of lung diseases in Hong Kong Special Administration Region. As from January 2001, the foundation shall award research grants, on an annual basis, to fund research projects being performed in the HKSAR. This aims to enhance the research culture and standards of local clinicians and health-care professionals in the field of respiratory medicine and related disciplines.

Please refer to the Hong Kong Lung Foundation Research grant regulations, which must be strictly adhered to. The completed application form and other required documents must be returned to the Honorary Secretary of Hong Kong Lung Foundation by 30th November of each year. Email submission is also acceptable and should be sent to: chanks@ha.org.hk.

Application procedures and application form of Research Grant can be downloaded from Hong Kong Lung Foundation Website: http://www.hklf.org/HKLF/research_grants_0304_e.htm

Hon secretary: Dr KS Chan, Pulmonary & Palliative Care Unit, Haven of Hope Hospital, Tseung Kwan O, Kowloon , Hong Kong. Fax: 2703 8799 Email: chanks@ha.org.hk

Hong Kong Lung Foundation Research Grant

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Pneumoconiosis Compensation Board (PCFB) Research Fund

The Pneumoconiosis Compensation Board (PCFB) set up a research fund in 1996 with the purpose to support projects that are related to the prevention, diagnosis, assessment of disability and treatment of pneumoconiosis in Hong Kong. Individual or group are invited to apply. Interested parties may visit the website: www.pcfb.org.hk or contact the PCFB at Tel: 2541 0032, Fax: 2541 0211 or Email: contact@pcfb.org.hk.

The Pneumoconiosis Compensation Board (PCFB) has recently established a training grant to facilitate health-care workers and occupational safety and health personnel to enhance their knowledge and skills in pneumoconiosis. This scheme aims to encourage eligible applicants to attend overseas training programmes or conferences that are related to the topic of pneumoconiosis. A maximum grant of HK$ 100,000 will be allowed for a suitable course longer than 6 months, and HK$ 50,000 for a course of 6 months or less. Interested applicants may contact the Board Secretariat, Trophy Mak at 2541 0032, or contact the PCFB at Tel: 2541 0032, Fax: 2541 0211 or E-mail: contact@pcfb.org.hk.

Pneumoconiosis Compensation Board (PCFB) Training Grant