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 16 Number 2 • Jun / Jul 2006

VVVVontents

Council Members (2005-2007) 1 HKTS and ACCP (HK & Macau Chapter)

Editorial Board 2 Editorial

2 Instruction to contributors

Clinical Meeting Summary 3 Recent Advances in Sleep Medicine Special Events

5 Scientific Roundtable Meeting: New Evidence in COPD

Special Articles 7 Anniversary Celebration of the Hong Kong Thoracic Society and the Hong

Kong Lung Foundation

Dissertation Abstracts 8

Practical Corner 16 Questions for the next issue

17 Ozone: what a chest physician should know?

20 What is the role of oral tyrosine kinase inhibitors in the management of

non-small cell lung cancer?

23 How to approach a patient who presents with lung mass?

Medical Statistics Corner 26 Medical Biostatistics

Book Review Column 31 Encyclopedia of Respiratory Medicine, Four-Volume Set

Diary of International Conferences 32

Forthcoming Clinical Meetings 33

Useful Websites

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Chest Full Text On-Line 35

Membership News 35

Funds and Grants 36

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Council of the Hong KongThoracic Society

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

PresidentDr MOK Yun Wing, Thomas

Vice-PresidentDr TAM Cheuk Yin

Honorary Secretary Dr CHAN Wai Ming

Honorary TreasurerDr HO Chung Man, James

Council MembersProf 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:Newsletter

Dr KO Wai San, Fanny

Address for CorrespondenceDr CHAN Wai Ming

Intensive Care Unit, Queen Mary HospitalPokfulam, 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 5 2 0 0 5 2 0 0 5 2 0 0 5 ---- 2 0 0 72 0 0 72 0 0 72 0 0 7

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X X X Xditorial 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

This issue of the Newsletter has reported 2 meetings, the Recent Advances in Sleep Medicine and the Scientific Roundtable Meeting: new evidence in COPD, organised by the Hong Kong Thoracic Society and the American College of Chest Physicians (HK and Macau Chapter). In this 20th anniversary year of the Hong Kong Thoracic Society and the 10th anniversary year of Hong Kong Lung Foundation, there will be a series of celbration events. We have listed these activities in this issue of the Newsletter and our members are most welcome to participate and to contribute.

Congratulations to the four doctors who have passed the respiratory exit examination and became Fellows in Respiratory Medicine recognised by the Hong Kong College of Physicians. Their dissertation abstracts are included in this Newsletter so that our members can also read their research work.

Finally, 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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linical Meeting Summary

Recent Advances in Sleep MedicineRecent Advances in Sleep MedicineRecent Advances in Sleep MedicineRecent Advances in Sleep Medicine

Drs David SC Hui and PC Wong

Co-chairmen of the Organizing Committee

A special clinical meeting on “Recent advances in Sleep Apnoea” was held on May 11, 2006 at the Four Seasons Ballroom, the New World Renaissance Hotel. This Clinical Meeting was organized by the Hong Kong Thoracic Society and the American College of Chest Physicians (Hong Kong and Macau Chapter). The organisers were very honoured and delighted to have a leading authority in Sleep Medicine, Prof. Neil J Douglas, to update us on Sleep Apnoea at the clinical meeting. Professor Douglas is the world renowned expert in the field of sleep apnoea with extensive publications in this area. He is currently the President of the Royal College of Physicians of Edinburgh and the Professor of Respiratory and Sleep Medicine at the University of Edinburgh. The Clinical Meeting was very well attended by more than 200 participants. Prof. Douglas had presented to the audience the most updated information on central and obstructive sleep apnoea from epidemiology, mechanisms, to treatment, pregnancy and sleep apnoea, and cardiovascular complications of sleep apnoea in his talk. There were also a lot of useful and stimulating discussions during the question and answer session.

Professor Neil J Douglas speaking at the Clinical Meeting “Recent Advances in Sleep Apnoea”.

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Dr. David Hui (Chairman, left) and Professor Neil Douglas (right) at the Clinical Meeting.

Professor Mary Ip (right) presented a souvenir to Professor Neil Douglas (left) at the meeting.

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pecial Event

Scientific Roundtable Meeting: New Evidence Scientific Roundtable Meeting: New Evidence Scientific Roundtable Meeting: New Evidence Scientific Roundtable Meeting: New Evidence in COPDin COPDin COPDin COPD

Drs Thomas Mok and PC Wong

Co-chairmen of the Organizing Committee

A Scientific Roundtable Meeting on new evidence in chronic obstructive pulmonary disease (COPD) was held on June 9, 2006 at the Renaissance Harbour View Hotel in Hong Kong. Twenty-five Council and Exco members of the Hong Kong Thoracic Society and the American College of Chest Physicians (Hong Kong and Macau Chapter) participated in this meeting. Professor Neil Barnes, Consultant Respiratory Physician from the London Chest Hospital of the United Kingdom presented the latest research findings on COPD. He emphasized the importance of inflammation in the pathogenesis of the disease and the anti-inflammatory effects of inhaled corticosteroid (ICS) and ICS/long acting beta-agonist (LABA) combination. He went on to present preliminary results of the TORCH (Towards a Revolution in COPD Health) study which examines the effect of salmeterol/fluticasone on the mortality of COPD patients. Prof Barnes’ talk was very well received with enthusiastic participation from members during the discussion time.

Professor Barnes speaking in the Scientific Roundtable Meeting: New Evidence in COPD

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Professor Barnes and members of the Hong Kong Thoracic Society and the American College of Chest Physicians (Hong Kong and Macau Chapter) at the meeting.

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pecial Article

Anniversary celebration of the Hong Kong Anniversary celebration of the Hong Kong Anniversary celebration of the Hong Kong Anniversary celebration of the Hong Kong Thoracic Society aThoracic Society aThoracic Society aThoracic Society and the Hong Kong Lung nd the Hong Kong Lung nd the Hong Kong Lung nd the Hong Kong Lung

FoundationFoundationFoundationFoundation

Drs Thomas Mok1 and Loretta Yam2

1. Chairman of the Hong Kong Thoracic Society

2. Chairman of the Hong Kong Lung Foundation

This is a special year for the respiratory community of Hong Kong. The year 2006 marks the 20th anniversary of the Hong Kong Thoracic Society and the 10th anniversary of the Hong Kong Lung Foundation. We are planning a series of events to celebrate our birth year : 1. Autumn Respiratory Seminar on September 24, 2006 2. Anniversary celebration dinner on September 23, 2006 3. Special edition of Newsletter of Hong Kong Thoracic Society and American College

of Chest Physicians (Hong Kong and Macau Chapter) in September 2006 4. Publication of a monograph on the history of Hong Kong Thoracic Society and the

Hong Kong Lung Foundation 5. Production of a memorial CD for the members of the Hong Kong Thoracic Society

and Hong Kong Lung Foundation 6. Activities to promote public education in respiratory health and diseases:

a. Walkathon b. A series of radio talks

Let’s celebrate and make 2006 a most memorable year for everyone of us.

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issertation Abstract

Smoking and tuberculosis among silicotic patients in Hong Smoking and tuberculosis among silicotic patients in Hong Smoking and tuberculosis among silicotic patients in Hong Smoking and tuberculosis among silicotic patients in Hong Kong Kong Kong Kong Dr. Ka-Wa Chan Tuberculosis and Chest Unit, Grantham Hospital Background Smoking and tuberculosis are both common conditions in Hong Kong. Silicotic patients carry a higher risk for tuberculosis. On the other hand, most of the silicotic patients are also smokers. Method A cohort of 431 silicotic patients with no history of tuberculosis was recruited from 1995 to 2002. Tuberculin test was done with 1 unit of PPD-RT23 and these patients were followed up prospectively till the end of 2004. Baseline background and disease characteristics were analysed with positive tuberculin reaction (>=10mm) and development of disease by univariate and then multivariate analysis. Results: Smoking and alcohol use were independent predictors of positive tuberculin reaction at baseline in multiple logistic regression analysis (all P < 0.05). Total cigarette pack-years did not demonstrate any significant effect. The annual incidences of tuberculosis were 1683, 2296 and 4392 for never, ex- and current smokers respectively. On Cox proportional hazard analysis, current smokers carried significantly higher risk of tuberculosis than other silicotic patients (adjusted hazard ratio: 1.93, 95% CI : 1.09-3.43) after controlling for age, alcohol use, tuberculin status, treatment for latent TB infection, and other relevant background / disease factors. A significant dose-response relationship was also observed with the number of cigarettes currently being smoked. Conclusion: Smoking increases the risk of both tuberculosis infection and the subsequent development of disease among silicotic patients. Smoking cessation may reduce the chance of developing TB in silicotic patients.

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issertation Abstract

A prospective study on the determinants of CPAP compliance A prospective study on the determinants of CPAP compliance A prospective study on the determinants of CPAP compliance A prospective study on the determinants of CPAP compliance in patients with obstructive slein patients with obstructive slein patients with obstructive slein patients with obstructive sleep apnoea syndrome ep apnoea syndrome ep apnoea syndrome ep apnoea syndrome Dr. Michael Chio-ho Chan Department of Medicine and Therapeutics, Prince of Wales Hospital Study Objectives To determine short-term and long-term compliance rates to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea and predictors for long-term CPAP compliance. Design To determine CPAP compliance and predictors for long-term CPAP compliance at 1 year after commencement of treatment. Setting A University Hospital. Patients One hundred and thirty one patients newly diagnosed with an apnoea-hypopnoea index (AHI) >= 10/hr on polysomnography. Interventions A CPAP device equipped with a time counter was used. Within the first year, patients were followed up at 4 weeks, 12 weeks, 26 weeks and 52 weeks. Measurements We evaluated the following factors for any correlation with objective CPAP compliance (machine run time [hours per day]) at 1 month, 3 months, 6 months and 1 year: demographic data, common OSA symptoms, baseline AHI, minimum arterial oxygen saturation (SaO2), mean SaO2, arousal index (AI), Epworth sleepiness scale (ESS), education level, CPAP levels, satisfaction with CPAP at the night of CPAP titration, side effects, and machine price. Results There were 109 males and 22 females , with a mean (± SD) age of 51.4 ± 9.4 yrs; body mass index 28.5 ± 3.9 kg/m2; AI, 28.4 ± 15.2/h; AHI, 40.4 ± 20.1/h; minimum SaO2 of 77.4 ± 10.2 %; mean CPAP pressure (95 %), 10.6+/-2.1 cmH20. Objective CPAP usage was 4.7 ± 2.0 h/d, 4.2 +/- 2.4 h/d, 4.3 +/- 2.3 h/d and 3.5 ± 2.4 h/d at 1, 3, 6 and 12 months, while 66.7% and 37.4% of our patients were using CPAP objectively for ≥4 h/d at 1 month and 1 year respectively. Following univariate analysis of variance, high baseline AHI (p = 0.003), obstructive apnea index (p=0.007), subjective compliance at 1st month (p <0.001) and objective compliance at 1st month (p <0.001) were associated with higher

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objective CPAP compliance at 12 months. Moreover, an equation involving the AHI and objective compliance at 1st month was developed for predicting the 12 months objective compliance with a correlation coefficient (r = 0.711).

Conclusion

CPAP usage and compliance were initially high in this patient population but decreased with time. A high baseline AHI, obstructive apnoea index, subjective /objective compliance at 1st month were the significant independent positive predictors of better CPAP compliance at 1 year.

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issertation Abstract

Evaluation of the British Thoracic Society rules (CURB and Evaluation of the British Thoracic Society rules (CURB and Evaluation of the British Thoracic Society rules (CURB and Evaluation of the British Thoracic Society rules (CURB and CURBCURBCURBCURB----65 seve65 seve65 seve65 severity scores*) in predicting communityrity scores*) in predicting communityrity scores*) in predicting communityrity scores*) in predicting community----acquired pneumonia with poor outcome in hospitalized acquired pneumonia with poor outcome in hospitalized acquired pneumonia with poor outcome in hospitalized acquired pneumonia with poor outcome in hospitalized patients patients patients patients Dr. Sik-nga Chan Department of Medicine, Tseung Kwan O Hospital

Study Objective The aim of this study was to evaluate CURB and CURB-65 severity scores in predicting community acquired pneumonia (CAP) with poor outcome. Risk factors associated with 30-day mortality due to CAP were assessed. Design Retrospective observational study Setting Department of Medicine, Tseung Kwan O Hospital, Hong Kong Patients Adult patients admitted to hospital with CAP in 2004 Measurements and results A total of 162 patients were included. The mean (median, range) age was 67.9 (72, 16-96) years. The overall mortality rate was 11.7%. Urea>7mmol/L, respiratory rate≥30/min, CURB score≥2 and CURB-65 score≥3 were associated with 30-day mortality, intensive care unit admission, ventilator support, prolonged length of stay, and newly need old age home arrangement. Systolic blood pressure<90mmHg increased the risk of 30-day mortality. Confusion was related to ICU admission and ventilator support while age≥65-year was associated with mortality and prolonged LOS. In multivariate analysis, respiratory rate≥28/min, systolic blood pressure<90mmHg, age≥80 years, albumin<30g/dL and multi-lobular involvement on chest radiograph were independent risk factors for 30-day mortality. Defining severe CAP as CURB severity score≥2, the 30-day mortality was 29.0%. By dividing the CURB-65 score into three risk groups (low mortality: 0-1, intermediate: 2, and high: 3-5), the mortality was 1%, 17% and 32% respectively. Conclusion Both CURB≥2 and CURB-65 score≥3 were associated with CAP with poor outcome in hospitalized patients. Respiratory rate≥28/min, systolic blood pressure<90mmHg, age≥80 years, albumin<30g/dL and multi-lobular

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involvement on chest radiograph were independent risk factors for 30-day mortality. * CURB-65 severity score was a 6 point scoring system, ranged from 0 to 5. Features included Confusion, Urea >7 mmol/l, Respiratory rate≧30/min, low Blood pressure (diastolic blood pressure (dBP) ≦60 mm Hg or systolic blood pressure (sBP) <90 mm Hg) and age ≧ 65years. One point was given for each feature present. Same calculation for CURB severity score, but age was not included, making for a range of 0-4 points.

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issertation Abstract

Role of endoscopic ultrasound in the staging and Role of endoscopic ultrasound in the staging and Role of endoscopic ultrasound in the staging and Role of endoscopic ultrasound in the staging and management of lung cancer management of lung cancer management of lung cancer management of lung cancer ------------ a literature review a literature review a literature review a literature review Dr. Kin-chung Ng Department of Medicine and Geriatrics, Caritas Medical Center

Lung Cancer is a leading cause of death among all diseases in developed countries, including Hong Kong. In 2000, there were 41.5 new cases of lung cancer per 100,000 population.1 Tumours with similar clinical outcomes are grouped under the same TMN stage, and each of these stages carries different prognosis and survival, and has different treatment strategies. As mediastinal lymph nodes are the most common site of metastases (75%) for regionally-advanced non-small cell lung cancer (NSCLC)2, a correct mediastinal nodal staging with histological diagnosis is crucial in our management of lung cancer.

Mediastinotomy and mediastinoscopy are well adopted as the “gold standard” for lung cancer staging as they can get a tissue diagnosis for pathological staging. Yet, they have the disadvantages of being invasive and require general anaesthesia. Computed tomography (CT) and positron emission tomography (PET) are alternatives for nodal staging, but they have their own limitations. Endoscopic ultrasound (EUS) has well-established values in the diagnosis and management of various gastrointestinal diseases. Since early 1980s, gastroenterologists have been exploring the role of EUS in nodal staging of lung cancers. For chest physicians, Kondo et al were the pioneers, with their first published series of 132 cases in 1990.3

Transoesophageal EUS can readily identify lymph nodes in the subcarinal, para-oesophageal and paratracheal regions, with pretracheal and intrapulmonary regions being the blind spots as ultrasound cannot penetrate through air-filled structures. Moreover, it can assess lymph nodes as small as 5mm4, and is superior to CT which can only visualize structures more than 1cm. Furthermore, EUS can obtain a tissue diagnosis rather than only an image by CT and PET scan. Only conscious sedation is required and is non-invasive as compared with thoracotomy. Overall, EUS-fine needle aspiration (FNA) has a sensitivity and specificity of 88 to 96% and 80 to 100% respectively.5 Varadarajulu et al also explored the role of transoesophageal EUS in staging of T4 lung cancer, with sensitivity and specificity of 87.5% and 98% in their study.6 In addition, as the negative predictive value of CT was 82%7, CT will miss 18% lung cancer patients with mediastinal diseases. Yet, using EUS, LeBlanc and Wallace could upstage the CT lung cancer staging and altered management in 25% of patients, avoiding them from unnecessary surgeries.8,9 On the other hand, high costs of the equipment involved, special training requirements and inaccessibility to anterior mediastinum are the potential limitations of transoesophageal EUS.

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The invention of endobronchial ultrasound (EBUS) and exploration of its role on lung cancer staging by Hurter and Hanrath in 1990 is an important breakthrough.10 EBUS-transbronchial needle aspiration (TBNA) allows real-time targeting of either mediastinal lymph nodes or lung lesions as compared with “blind” biopsy of traditional TBNA. The use of small-gauze needles minimizes risks of procedure-related bleeding. Puncturing blood vessel between bronchial wall and the lesion can be avoided by pre-biopsy Doppler examination. EBUS is particularly useful for evaluation of anterior mediastinal lymph nodes, and can access lymph nodes as small as 5mm in short axis in close proximity to major vessels.11 In addition, it is a safe procedure and can be done on out-patient basis without need of general anaesthesia.

Anatomically, transoesophageal EUS and EBUS-TBNA are complimentary to each other, so both anterior and posterior mediastinal lymph nodes can be assessed together. Rintoul el al and Vilmann’s group showed that accuracy of mediastinal nodal staging could be improved to 100% if both procedures were performed.12,13 EUS-FNA also allows us to get minimal tissue for detection of micrometastases in mediastinal lymph nodes. Such molecular staging by detecting tumour markers such as Muc 1, lunx and telomerase has important implications in terms of tumour prognosis and choice of treatment. In conclusion, EUS-FNA and EBUS-TBNA are well proven to have high sensitivity and specificity in lung cancer mediastinal staging. Still, most endoscopists doing EUS and EBUS are on their learning curves, and such technology has not been widely adopted as initial step of lung cancer staging. The availability of resources is another important issue. With the publications of more large-scale prospective studies on EUS and EBUS, we hope that these 2 technologies can play an early and essential step in lung cancer staging in the near future.

References: 1. Hong Kong Cancer Registry 2000. 2. Ries LA, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review, 1975-2001. Bethesda, National Caner

Institute, 2001. 3. Kondo D, Imaizumi M, Abe T, Naruke T, Suemasu K. Endoscopic ultrasound examination for mediastinal

lymph node metastases of lung cancer. Chest 1990; 98: 586-593. 4. Vilmann P. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lymph nodes. Gastrointest

Endosc 1996; 43: S24-29. 5. Savoy AD, Ravenel JG, Joffman BJ, et al. Endoscopic ultrasound for thoracic malignancy: a review. Curr Probl

Diagn Radiol 2005; 34: 106-115. 6. Varadarajulu S, Schmulewitz N, Wildi SM, et al. Accuracy of EUS in staging of T4 lung cancer. Gastrointest

Endosc 2004; 59: 345-348. 7. Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the

current evidence. Chest 2003; 123: 137S-146S. 8. LeBlanc JK, Devereaux BM, Imperiale TF, et al. Endoscopic ultrasound in non-small cell lung cancer and

negative mediastinum on computed tomography. Am J Respir Crit Care Med 2005; 171: 177-182. 9. Wallace MB, Ravenel J, Block MI, et al. Endoscopic ultrasound in lung cancer patients with a normal

mediastinum on computed tomography. Ann Thorac Surg 2004; 77: 1763-1768.

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10. Hurter T, Hanrath P. Endobronchial sonography in the diagnosis of pulmonary and mediastinal tumours. Dtsch Med Wochenschr. 1990; 115(50): 1899-1905.

11. Yasufuku K, Chiyo M, Koh E, et al. Endobronchial ultrasound guided transbronchial needle aspiration for staging of lung cancer. Lung Cancer 2005; 50: 347-354.

12. Rintoul RC, Skwarski KM, Murchison JT, et al. Endobronchial and endoscopic ultrasound-guided real-time fine-needle aspiration for mediastinal staging. Eur Respir J 2005; 25: 416-421.

13. Vilmann P, Krasnik M, Larsen SS, et al. Transoesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy: a combined approach in the evaluation of mediastinal lesions. Endoscopy 2005; 37: 833-839.

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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 clinical applications of proportional assist ventilation. (from Dr. WC Wong, Kwong Wah Hospital)

2. What is the potential role and diagnostic utility of medical thoracoscopy?

(from Dr. WL Law, Queen Elizabeth Hosptial)

3. How is bone scan compared with PDG-PET in the evaluation of

bony metastases in lung cancer? (from Dr. Matthew Wong, Queen Mary Hospital)

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ractical Corner

Ozone: what a chest physician should know? Ozone: what a chest physician should know? Ozone: what a chest physician should know? Ozone: what a chest physician should know? Dr. Henry Kwok Department of Medicine, Ruttonjee Hospital

To answer this question it should first be made clear that the ozone (O3) from the stratosphere has different function as that from the troposphere. The earth’s atmosphere can be divided into various layers. The layer of air from sea level upwards to a height of 10-17km is designated troposphere, while the layer from 17 to about 50 km is designated stratosphere. Beyond that the layer of the atmosphere is designated as the mesosphere (Figure 1).

Figure 1. The layers of the atmosphere

Earth

Trophsphere

Stratosphere

Mesosphere

50 km above sea level

10-17 km above sea level

Sea level

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O3 in the stratosphere is protective to the health of humans by shielding the earth from ultraviolet (UV) light of cosmic origin. The O3 holes that result from overuse of ozone destroying chemicals, like the chlorofluorocarbons (CFC) used as older generation propellants in metered dose inhalers, allow the UV radiation to reach the earth with adverse health consequences like skin cancers.

However, O3 in the troposphere is regarded as an air pollutant. It is formed as a secondary pollutant from the combination of oxygen (O2) and oxygen free radical (O•). The oxygen free radical is formed from the splitting of nitrogen dioxide (NO2) catalysed by ultraviolet light. NO2 is of course a primary air pollutant formed from various sources like combustion engines and car exhaust. Normally O3 will be reverted back to O2 by combining with NO, which is another lytic product of NO2, back to form NO2. However, in certain circumstances like the presence of atmospheric hydrocarbons (HC), the NO is directly reverted to NO2 thus bypassing the reaction with O3 (Figure 2). The result is the accumulation of O3 in the trophsphere leading to adverse health effects.

Adverse health effects of ozone It should be noted that O3 is much more reactive than NO2 in causing adverse health effects. When exposed to O3, the human body will show evidence of local irritation in the airway with secondary infections. This is related to the action of O3 on fatty acids through a process called lipid peroxidation. As the cell membranes are largely composed of lipids, disruption of cell membranes among different cell types will lead to different consequences due to cellular dysfunctions. For example, for alveolar macrophages, disruption of cell membranes will lead to dysfunction of macrophages as an antigen presenting cells, thus weakening the airway defence mechanisms. The result is thus increased probability of pneumonia, and this is exhibited in a dose response manner among animal models challenged with aerosolized Streptococcus after pre-treatment with different concentrations of ozone. On the other hand, O3 will also activate polymorphonuclear cells leading to generation of reactive oxygen species and hypochloric acid (HOCl), thus leading to airway inflammation and destruction of lung tissues. Furthermore, O3 will also

Source-- eg engines

NO2

NO + O•

O3 O2

O2

HCO2

O2 + HC

Accumulate

Figure 2. Photolytic cycle and the accumulation of ozone

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inactivate alpha-1 antitrypsin in a manner similar to cigarette smoke and further lead to lung tissue destruction. The net result is thus an overall airway inflammation with secondary infections, and in the long term, lung fibrosis and loss of lung tissues.

References: Nadakavukaren A (editor). Our Global Environment. A Health Perspective , 5th edition. Waveland Press Inc. Gilmour MI, Park P, Selgrade MK. Ozone-enhanced pulmonary infection with Streptococcus zooepidemicus in mice. The role of alveolar macrophage function and capsular virulence factors. Am Rev Respir Dis 1993; 147(3):753-60.

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ractical Corner

What is What is What is What is the role of oral tyrosine kinase inhibitors in the the role of oral tyrosine kinase inhibitors in the the role of oral tyrosine kinase inhibitors in the the role of oral tyrosine kinase inhibitors in the management of nonmanagement of nonmanagement of nonmanagement of non----small cell lung cancer? small cell lung cancer? small cell lung cancer? small cell lung cancer? Dr. Stephanie YY Chu Department of Medicine, Queen Elizabeth Hospital

Lung cancer remains the top killers for both men and women in Hong Kong.1 Over half of these patients have non-small cell lung cancer (NSCLC) with a significant proportion presents at advanced stages where only palliative treatment can be offered. Chemotherapy can be recommended for advanced NSCLC, which has been shown to improve symptom control as well as survival over best supportive care in patients with good performance status.2 However, some patients with advanced NSCLC cannot receive chemotherapy either because of advanced age, poor performance status, presence of multiple comorbidities or patient refusal. Advances in understanding of cancer cell biology have led to the discovery of key molecular pathways that drives tumor growth. One such pathway is initiated by activation of the epidermal growth factor receptor (EGFR). The epidermal growth factor receptor (or Erb1) is a member of the ErbB family of transmembrane tyrosine kinase receptors. Increased expression of EGFR is seen in various solid tumours including NSCLC where over-expression has been reported in 40-80% of cases.3 In contrast to chemotherapeutic agents which affect all dividing cells, agents targeting the EGFR act selectively on malignant cells with a very limited role in normal non-embryonic tissue. Thus these agents have a potential for less treatment-associated toxicity compared with the nonspecific cytotoxic drugs.4 Tyrosine Kinase Inhibitors Several EGFR inhibitors have been developed and can be divided into mainly two classes: small molecules that are inhibitors of the intracellular tyrosine kinase (TKI) domain by interfering with autophosphorylation via adenosine triphosphate (ATP), or monoclonal antibodies to the extracellular domain of the EGFR.5 Currently there are two orally active TKI agents available on the market for treatment of NSLC, namely Gefitinib (Iressa) and Erlotinib (Tarceva). Both play an important role as second-line palliative chemotherapy in patients with advanced NSCLC. Gefitinib Two phase II trials (IDEAL-1 and IDEAL-2) demonstrated that gefitinib was able to induce tumour regression in approximately 10-20% patients with recurrent disease previously treated with chemotherapy. In addition, tumour-related symptoms also improved in approximately 35-40% of patients. The median duration of response was 6-7 months.6,7 Amongst those patients who had improvement in their symptoms, 68-75% of responses were seen within the first month of treatment.6,7 Further randomized phase III clinical trials (INTACT I and II)8,9 looking at the effect of adding gefitinib to standard platinum-based

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chemotherapy in chemotherapy-naïve patients with advanced NSCLC failed to show any added benefit. More disappointingly, the large phase III post marketing ISEL trial (Iressa Survival Evaluation in Lung cancer) showed that there was no survival benefit in patients with advanced NSCLC treated with Iressa as second or third line therapy against best supportive care.10 However there was suggestion of a longer survival in certain subgroups of patients who were never smokers,6,10 Asians,10 women6 and those with adenocarcinoma.6 Specific mutations in the EGFR gene were also shown to correlate with clinical responsiveness with gefitinib.11

Erlotinib Erlotinib is another TKI with slightly different pharmacologic characteristics. In a phase II study involving patients with previously chemotherapy treated NSCLC, a response rate of 12.3% was seen. Survival was correlated to the occurrence and degree of skin toxicity, and there was no relation to EGFR expression.12 Subsequently, a randomized double-blind phase III trail studying patients with stage IIIB or IV NSCLC who had received one or two prior chemotherapy regimes, the response rate with Erlotinib was 8.9% compared with less than 1% in the placebo group (P<0.001). Overall survival was also significantly better in the Erlotinib group (6.7 vs. 4.7 months, p value <0.0001) and the median duration of response was 7.9 months. Quality of life analysis showed that patients treated with Erlotinib had better improvement in symptom control such as cough, pain and dyspnoea. The likelihood of a response to Erlotinib was higher amongst women, non-smokers, Asians and patients with adenocarcinoma.13 Survival was not influenced by EGFR expression or mutation, though a response was more likely with EGFR expression.14 Summary Tyrosine kinase inhibitors is a potentially important group of agents used in second or third-line chemotherapy for advanced non-small cell lung cancer, with a more favourable response in selected groups of patients. Their role as first-line agent, especially in the Asian population remains to be determined.

References: 1. Hong Kong Cancer Registry 2. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-

analysis using updated data on individual patients from 52 randomised clinical trial. BMJ 1995;311:899-909. 3. Salomon DS, Brandt R, Ciardiello F, et al.Epidermal growth factor-related peptides and their receptors in

human malignancies. Crit Rev Oncol Hematol 1995; 19:183-232. 4. Silvestri GA and Rivera MP. Targeted therapy for the treatment of advanced non-small cell lung cancer: A

review of the Epidermal Growth Factor Receptor Antagonist. Chest 2005; 128:3975-3984. 5. Giacocone G. Epidermal Growth Factor Receptor Inhibitors in the treatment of non-small cell lung cancer. J

Clin Oncol 2005; 23:3235-3242. 6. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor

receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003; 290:2149-58.

7. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small cell lung cancer (the IDEAL Trial) J Clin Oncol 2003;21:2237-46 (Erratum, J Clin Oncol 2004; 22:4811).

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8. Giaccone G, Herbst RS, Manegold C, at al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small cell lung cancer: a phase III trial—INTACT 1. J Clin Oncol 2004; 22:777-84.

9. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small cell lung cancer: a phase III trial—INTACT 2. J Clin Oncol 2004;22:785-94.

10. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005; 366 (9496):1527-37.

11. Lynch T, Daphne WB, Rafaella S, et al. Activating mutations in the Epidermal Growth Factor Receptor underlying responsiveness of Non-small cell lung cancer to Gefitinib. N Engl J of Med 2004; 350:2129-39.

12. Perez-Soler R, Chachoua A, Hammond LA, et al. Determinants of tumour response and survival with Erlotinib in patients with non-small cell lung cancerJ Clin Oncol 2004; 22:3238-3247.

13. Shepherd FA, Pereira JR, Ciuleanu T, et al. Erlotinib in Previously Treated Non-small cell lung cancer. New Engl J Med 2005; 353:123-32.

14. Tsao M-S, Sakurada A, Cutz J-C, et al. Erlotinib in Lung Cancer—Molecular and Clinical Predictors of Outcome. N Engl J Med 2005; 353:133-144.

23

ractical Corner

How to approach a patient who presents with lung mass? How to approach a patient who presents with lung mass? How to approach a patient who presents with lung mass? How to approach a patient who presents with lung mass?

Dr. Joan P.C. Fok Department of Medicine and Therapeutics, Prince of Wales Hospital

Every day, in our clinics and in-patient rounds, we encounter patients with abnormal lung shadows. Lung shadow with a diameter less than or larger than 3 cm are termed lung nodule and mass respectively. The differential diagnoses include neoplastic, infective, inflammatory, vascular and other causes. Attempts to use logistic prediction model to identify malignant lung nodules failed to show improvement in diagnostic accuracy than physician’s predictions1. In our local hospital setting, there is no standard diagnostic algorithm and every case is individually evaluated. History and physical examination are essential components in our assessment. Patient characteristics such as history of smoking, age ≥ 50 years, significant weight loss, jaundice, history of malignant disease, monocytes > 7% and platelet count > 440 x 10 9/ l are associated with higher likelihood of malignancy.2-4

The investigation of choice depends on the clinical condition of the patient, the technology available and the patient’s preference. Computed tomography (CT) thorax remains helpful in visualization of the size, shape and appearance of the lung lesion. Lung mass of larger size has a higher likelihood of malignancy.3,4 Nonetheless, in the . Early Lung Cancer Action Project (ELCAP) study, 63% of the carcinoma detected was less than 11 mm in diameter.4 As the health awareness of the general public is increasing, many people are keen for radiological screening for malignancy although it has not been shown to decrease mortality. We, as clinicians, should be careful in managing asymptomatic patients who present with small lung nodules. Shape of the lung mass gives us clues to the nature of the lesion. Smooth border suggests benignity with the exception of carcinoid and solitary metastasis. Spiculated or lobulated border suggests malignancy. Presence of a feeding vessel suggests arteriovenous malformation. Presence of satellite lesions suggests granulomatous disease. The internal density of the lesion is best seen on CT thorax. Central, diffuse, laminated and popcorn appearance are all benign patterns of calcification whereas eccentric or amorphous calcification are suspicious of malignant process. The presence of air bronchogram are seen in 20-30%of malignant lesions and in <10% of benign nodules. The presence of ground glass appearance are suggestive of adenocarcinoma and bronchioloalveolar carcinoma.5,6 Growth of the lesion should be monitored. Benign lesions have doubling times (a 25% increase in diameter of the lesion on CT scan ) of less than 1 month or greater than 18 months.1 Doubling time between 1 and 18 months suggests malignant cause and warrants further evaluation. In all cases, we should make an effort to trace old films for comparison.

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Positron Emission Tomography (PET scan) is another imaging modality which has the advantage of picking up distant metastasis in malignancy. Specific uptake ratio (SUV) > 2.5 suggests malignancy. It does not carry radiation hazard nor contrast risks. When assessing lesions > 10 mm in diameter, it has a sensitivity of 94% and a specificity of 88%.7,8 The drawback is the confusing information obtained in case of false negatives and positives. A metabolically active lesion such as active Tuberculosis can have high uptake on PET scan. False negatives include poorly controlled diabetes, carcinoid, bronchioalveolar carcinoma and lesions less than 1cm in diameter. Definitive diagnosis relies on histopathological diagnosis. Sputum should be collected for cytology and culture examination. In the diagnosis of malignancy, it has been found that sputum cytology has a pooled sensitivity of 0.66 ( 0.71 for central lesions and 0.49 for peripheral lesions ) and specificity of 0.99.9 Bronchoscopy has a diagnostic yield which range from 40-90%. The yield of bronchoscopy is related to size, location and the margin of the lesion. Larger, central and lesion with irregular edge have higher yield.9-11 The use of endobronchial ultrasound has been shown to increase the yield of peripheral small lesions.12-13 CT-guided fine needle aspiratory for cytology (FNAC) of lung is helpful in diagnosing peripheral lung lesions. However, it carries risk of pneumothorax and the sample size is small. In patients with good lung function, surgical biopsy of undiagnosed lung mass should be considered. Video-assisted thoracoscopic surgery is widely practiced and it carries low morbidity and mortality. To conclude, management plan of the lung mass should be individually made, based on characteristics of the lesion, patient and available resources. A lesion which remains unchanged for 2 years is generally, but not always, benign. Biopsy remains the definitive diagnosis and clinicians should be vigilant in different investigation options.

References: 15. Swensen SJ, Silverstein MD, Edell ES, et al. Solitary pulmonary nodules: Clinical prediction model versus

physician. Mayo Clinic Proceedings 1999; 74(4):319-329. 16. Midthun DE, Swenson SJ, Jett JR. Approach to the solitary pulmonary nodule. Mayo Clinic Proceedings 1993;

68(4):378-85. 17. Weiser MA, Cabanillas M, Vu K, et al. Diagnostic evaluation of patients with a high suspicion of malignancy:

comorbidities and clinical predictors of cancer. Am J Med Sci 2005: 330(1):11-18. 18. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and

findings from baseline screening. Lancet 99; 354:99-105. 19. Ost D, Fein AM, Feinsilver SH. The Solitary Pulmonary Nodule. New England Journal of Medicine 2003;

348(25):2535-42. 20. Zwirewich CV, Vedal S, Miller RR, et al. Solitary pulmonary nodule: high-resolution CT and radiologic-

pathologic correlation. Radiology 1991; 179:469-476. 21. Schrevens L, Covent N, Dooms C, et al. The Role of PET Scan in diagnosis, staging and management of Non-

Small Cell Lung Carcinoma. The Oncologist, 2004; 9(6): 633-643. 22. Chhajed PN, Bernasconi M, Gambazi F, et al. Combining bronchoscopy and positron emission tomography for

diagnosis of the small pulmonary nodule ≤ 3 cm. Chest 2005; 128:3558-3564. 23. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung

cancer. Summary of published evidence. Chest 2003; 123:115s-128s. 24. Baaklini WA, Reinoso MA, Gorin AB, et al. Diagnostic Yield of fibreoptic bronchoscopy in evaluating solitary

pulmonary nodules. Chest 2000; 117: 1049-1054.

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25. Vijay C. Bronchoscopy diagnosis of solitary pulmonary nodules and lung masses in the absence of endobronchial abnormality. Chest 1996; 109: 620-625.

26. Herth FJF, Eberhardt R, Becker HD, et al. Endobronchial ultrasound-guided transbronchial lung biopsy in fluoroscopically invisible solitary pulmonary nodules. A prospective trial. Chest 2006; 129(1):147-50.

27. Kikuchi, E, Yamazaki, K, Sukoh N, et al. Endobronchial ultrasonography with guide-sheath for peripheral lung lesions. Eur Resp J 2004: 24:533-537.

26

edcial Statistics Corner

Medical Biostatistics Medical Biostatistics Medical Biostatistics Medical Biostatistics

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

Evaluation of Diagnostic Test Accuracy Tests as diagnostic aids are key element of clinical medicine, where diagnostic criteria and/or tests are often used to establish the presence and absence of a risk factor and outcome of a disease status. For instance, ECG , cardiac enzymes for diagnosis of myocardial infarction; murphy’s sign in diagnosis of acute cholecystitis; or Pap smear for detection of cervical cancer. Very often, definitive diagnosis may be difficult or impossible to obtain, as “ Gold standard ” may be expensive, inappropriate (e.g. autopsy based) or unsuitable(e.g. clinical follow up when immediate decision is required) . Alternative tests may serve as surrogates but this requires that they be appropriately validated against a suitable gold standard, and that their properties be documented.

The goal of these tests is to minimize misclassification. Ideally, we want tests that only give true positive and true negative results, yet some misclassification may be inevitable for logistical reasons. Therefore, in real life, extent and influence of false positive and false negative findings have to be considered before decision making.

In the end of this chapter, we shall be able to do the followings: 1. Understand the 2x2 table of disease and test status. Know what is misclassification, and understand why misclassification is inevitable under most circumstances? 2. Define and calculate sensitivity, specificity, positive predictive value (PPV) and negative predictive values( NPV). 3. Understand the influence of prevalence and/or pretest probability on predicted values. 4. Understand the pitfalls in assessment of diagnostic test performance.

1. What is a 2x2 Table of Disease and Test status? What is misclassification and why are they unavoidable?

We can use a 2x2 table to describe the various possibilities of disease and test outcomes. This table underlies the basic principles of test evaluation:

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Disease + Disease – Test + True positive (TP) False positive (FP) Test - False negative (FN) True negative (TN)

In real life, test results of disease and non-disease (or normal) status are available as 2 spectrums of value which always overlap to certain extent (Figure 1) . The degree of overlapping actually depends on the characteristics of the subjects being recruited for test validation, and it is this overlapping condition that makes misclassification inevitable. In practice, classification of a test status using a cutoff value is essential for us to establish a diagnosis. This value is based on a cutpoint along a continuum of values where the spectrums overlap, and it can be chosen anywhere along it. However, there is always a tradeoff between the two.

Figure 1.α & β represent those subjects being misclassified. α = false positive β = false negative

Adjusting the cutpoint between µN & µD result in different α& β, as well as varying true positive and true negative values. The choice of cutpoint depends on the relative adverse consequences of false negatives versus false positives. If it is most important not to miss anyone, use cutpoint that increases sensitivity and decrease specificity. If it is most important that people not be erroneously labeled as having the condition, use one that decreases sensitivity and increases specificity.

2. How to define and calculate sensitivity , specificity , positive predictive value (PPV) and negative predictive values( NPV)?

Sensitivity = P (T+ / D+) = probability of those tested positive among the disease

= TP/ (TP+FN) = true positive rate

Specificity = P (T- / D-) = probability of those tested negative among the non-disease = TN/ (TN+FP) = true negative rate

Complementary probabilities: False negative rate = FN/( TP+FN) = P(T-/D+) = 1-sensitivity False positive rate = FP/ ( TN+FP) = P( T+/D-) = 1-specificity

Sensitivity and specificity are characteristics of a particular test that are compared to gold standard measurements, and their meanings are based on

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knowledge of gold standard results. No matter how superior these test characteristics are, they cannot be directly applied for use in clinical judgment and decision making. In practice, our clinical judgement is based on a test status, instead of a gold standard finding. For interpretation, we need to know how likely is a patient really having the disease if the test result is positive and how likely is he/she disease free should the result be negative. Conceptually, they are different from sensitivity and specificity.

Positive predictive value = P( D+/ T+) = probability of a patient having the disease among those tested positive = TP / (TP+FP) Negative predictive value = P (D- / T-) = probability of a patient not having the disease among those tested negative = TN/ (TN+FN) The positive and negative predictive values depend on the pretest probability of the condition of interest , in addition to the sensitivity and specificity of the test. This pretest probability is often the prevalence of the condition in the population of interest.

Example 1: A researcher develops a new saliva pregnancy test. She collects samples from 100 women known to be pregnant by blood test (gold standard ) and 100 women known not be pregnant, also based on the same blood test. The saliva test is “positive” in 95% of the pregnant women. It is also “positive” in 15 of the non-pregnant women. 1. What are the sensitivity ,specificity, positive predictive value and negative predictive value ? 2. Is it more important that a test be sensitive or specific? Construct 2x2 table of test and disease status Pregnant Non-pregnant Totals

Saliva+ 95 15 110 Saliva- 5 85 90 Totals 100 100 200

Sensitivity = Saliva+/ Pregnant = 95/100 = 95% Specificity = Saliva-/ Non-pregnant = 85/100 = 85% PPV = Pregnant/ Saliva+ = 95/110 = 86% NPV = Non-pregnant/ Saliva- = 85/90 = 94% Whether sensitivity or specificity is more important depends on purpose of the particular test. A cheap mass screening pregnancy test should emphasize on sensitivity so that only few cases are missed ( few false negatives). Whereas a

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test designed to confirm the presence of pregnancy should be specific so as to minimize cases wrongly diagnosed ( few false positives).

3.What is the influence of prevalence and/or pretest probability on predicted values ? Positive predictive value P( D+/ T+) = TP / (TP+FP) = sensitivity x prevalence of disease (sensitivity x prevalence of disease)+(1-specificity)( 1- prevalence of disease) Negative predictive value P ( D-/T-) = TN/ (TN+FN) = specificity x ( 1- prevalence of disease) (specificity x ( 1- prevalence of disease))+(1-sensitiviy )( prevalence of disease) Example 2: The saliva pregnancy test is administered 30 days after the first day of the last menstrual period to 2 groups of women who have thus far “ missed ‘ a period. Group 1: 1000 sexually active young women using no contraception. Pretest probability of pregnancy 40% (hypothetical) Based on sensitivity of 95% , expected TP = 1000 x 0.4x 0.95 = 380 Expected FN = 1000 x 0.4 – 380 = 20 Based on specificity of 85%, expected TN= 1000 x 0.6 x 0.85 = 510 Expected FP = 1000 x 0.6 - 510 = 90 2X2 table Pregnant Non-pregnant Totals Test + 380 90 470 Test- 20 510 530 Totals 400 600 1000 Positive predictive value = TP/ (TP+FP) = 380/470 = 81% In this context, a woman with a positive saliva test has an 81% chance of being pregnant. Negative predictive value = TN/(TN+FN) = 510/530 = 96% In this context, a woman with a negative saliva test has a 96% chance of not being pregnant ( and a 4% chance of being pregnant) Group 2: 1000 oral contraceptive users, pretest probability of pregnancy = 10% Using sensitivity = 95% , expected TP = 1000 x 0.1x 0.95 = 95 Expected FN = 1000 x 0.1 – 95 = 5 Using specificity = 85%, expected TN= 1000 x 0.9 x 0.85 = 765 Expected FP = 1000 x 0.9 - 765 =135

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2X2 table Pregnant Non-pregnant Totals Test + 95 135 230 Test- 5 765 770 Totals 100 900 1000 In this context , Positive predictive value is only 95/230 = 41% Negative predictive value = 765/770 = 99% From the examples, we can appreciate how the pretest probability of the condition affects the PPV and NPV of a test.

4. What are the pitfalls in assessment of diagnostic test performance? 1. Recognise the importance of pretest probability/ prevalence of disease on predictive values. For example, the predictive values of PET scan on diagnosing lung cancer for solitary pulmonary nodule (SPN) are different in areas with high prevalence of tuberculosis and that with low prevalence, as TB is one of the most important competing causes with lung cancer in cases of SPN. 2. Should the test becomes widely applicable to the general population, the pretest probability and predictive values cannot ordinarily be extrapolated from a validation study, since the proportions with and without the disease in the validated sample are determined by the investigator, rather than a genuine reflection of disease prevalence in the general population. 3. Sensitivity and specificity estimates do not depend on the prevalence of the condition in question. But their values and their validity depend on the context in which they are derived, and this context in turn affect the predictive values. 4. It is important to know about the characteristics of sample used for test validation, and how similar is this sample to the situation in which the test will be applied. Application of the test to a population with characteristics entirely different from that of the validation sample will result in altered test sensitivity and specificity.

References: 1. Armitage P, Berry G. Statistical Methods in Medical Research. Third Edition. Blackwell Science 2. Hennekens, Burring. Epidemiology in Medicine. Lippincott Williams & Wilkins. 3. Allard R, Bourbeau J, Menzies D, Schwartzman K. Epidemiology : Principles and Methods. Department of

Epidemiology and Biostatistics, McGill University, Canada

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Name of the book: Encyclopedia of Respiratory Medicine, Four-Volume Set (Volume 1-4) Publisher: Elsevier Publication date: April 5, 2006 Editors: Geoffrey Laurent, Steven Shapiro ISBN: 0-12-438360-2

A

ook Review Column

four-volume work that provides an authoritative and comprehensive coverage of the complete field of respiratory medicine. It provides a vital

interface between the pure and clinical science environments covering all aspects of respiratory medicine from the relevant molecular biology to the treatment of diseases that affect the respiratory system. It includes comprehensive coverage of lung cells, the structural components of the lung and key molecules that regulate lung function as well as all the major respiratory diseases. Students, researchers and professionals alike will find this an authoritative source of information on all aspects of respiratory medicine.

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.

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iary of International Conferences

2-6 September, 2006 Munich Denmark

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

21-26 October, 2006 Salt Lake City U.S.A

CHEST 2006 Info: www.chestnet.org/CHEST

20-23 November, 2006 Kyoto Japan

11th Congress of the APSR Info: www.APSResp.org

29 -31January, 2007 San Diego USA

43rd Annual Meeting of The Society of Thoracic Surgeons Info: www.sts.org

Email: sts@sba.com

23-27 February, 2007 San Diego, USA

63rd Annual AAAAI Meeting Info: http://www.aaaai.org/members/meetings/future_meetings.stm

23-28 March, 2007 Auckland New Zeland

TSANZ ASM Info: www.thoracic.org.au

10-12 May, 2007 Tokyo Japan

47th JRS Meeting Info: www.jrs.or.jp

E mail: 47jrs@jrs.or.jp

18-23 May, 2007 San Francisco USA

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

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

July 27, 2006

Clinical meeting by Queen Elizabeth Hospital and Kowloon Hospital

Venue: Lecture Theatre, Ruttonjee Hospital

Time: 6:30pm

September 24, 2006 Autumn Respiratory Seminar

Venue: Hong Kong Convention and Exhibition Centre

November 16, 2006 Clinical meeting by Princess Margaret Hospital

and Caritas Medical Center

Venue: Lecture Theatre: Ruttonjee Hospital

Time: 6:30pm

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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 May 11, 2006, there are 729 Members (196 Ordinary members, 6 Honorary members, 66 Life members and 461 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.

♦ For membership renewal, 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 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