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

Newsletter

Circulation restricted to members only

Volume 17 Number 1 • Mar/ Apr 2007

Vontents Council Members (2007-2009)

1 HKTS and ACCP (HK & Macau Chapter) Editorial Board

Editorial 2 Instruction to contributors

Annual Scientific Meeting 2007 3

Clinical Meeting Summary 7 Therapeutic Drug Monitoring And Tuberculosis 9 “What Lies Beneath”

Special Events 15 Asthma Symposium

Practical Corner 16 Questions for the next issue 17 What are the physiologic changes involved in high altitude? 20 What is tracheobronchomalacia? 25 What environmental hazards are present for the air travellers with

respiratory problems and what are the possible measures? Medical Statistics Corner

29 Medical biostatistics Book Review Column

33 AACN Protocols for Practice: Non-invasive Monitoring Diary of International Conferences 34 Forthcoming Clinical Meetings

35 Useful Websites

36 Chest Full Text On-Line

37 Membership News

37 Funds and Grants 38

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HHHKKKTTTSSS

AAACCCCCCPPP

Council of the Hong Kong Thoracic Society

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

PresidentDr CHAN Wai Ming

Vice-PresidentDr KO Wai San, Fanny

Honorary Secretary Dr TAM Cheuk Yin

Honorary TreasurerDr HO Chung Man, James

Council MembersDr MOK Yun Wing, Thomas

(Ex-President)Prof LAM Wah Kit

Prof IP Sau Man, Mary Dr LAI Kei Wai, Christopher

Dr YU Wai ChoProf TSANG Wah Tak, Kenneth

Prof HUI Shu Cheong, DavidProf CHAN Mo Wah, Moira

Dr PANG Joseph Dr HO Sheng Sheng

Dr YEE Kwok Sang, WilsonDr TSE Pak Yiu

Dr CHUI Wing HungDr WONG Kam Cheung

Dr LO Ho Yin

Chief Editor:NewsletterDr SO KY Loletta

Address for CorrespondenceDr TAM Cheuk Yin

Department of MedicineTuen Mun Hospital

Tuen Mun, HK

President Dr CHU Chung Ming

Vice-President Dr CHAN Wai Man, Johnny

Honorary Secretary/Treasurer Dr WONG Mo Lin, Maureen

Executive Committee Members Dr WONG Poon Chuen (Ex-President) Prof LAM Wah Kit Dr CHAN Hok Sum Dr LAM Chak Wah Dr TAM Cheuk Ming Dr CHOO Kah Lin Dr KWOK Kai Him, Henry Dr LAU Chun Wing Dr Wong Chi Fong Dr LAM Bing

Governors Dr CHAN Kin Sang Dr MOK Yun Wing, Thomas Dr YEW Wing Wai

Regent Prof IP Sau Man, Mary

Address for Correspondence Dr WONG ML Maureen Department of Medicine, Caritas Medical Centre, Hong Kong

2 0 0 7 - 2 0 0 9

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Xditorial Board

Editor

Dr Loletta KY SO

Deputy Editor Dr Johnny CHAN

Immediate Past Editor

Dr Fanny WS KO

Board Members Dr Sheng Sheng HO

Dr Henry KWOK Dr Yuk Lung KWOK Dr David CL LAM Dr Wai Kei LAM

Dr Arthur CW LAU Dr Man Po LEE Dr Julie WANG

Dr Matthew K Y WONG Dr Wilson K S YEE

Miss Amon YP LAM Miss Barbara LAW Miss Mary TSANG

Address for Correspondence

Dr Loletta So Dept. of Medicine

Pamela Youde Nethersole Eastern Hospital

Chai Wan Hong Kong

Fax

(852) 2515 3182

Email soky@ha.org.hk

Editorial _______________________________

The Hong Kong Thoracic Society and the American College of Chest Physicians (Hong Kong and Macau chapter) have recently elected new Councils for 2007–2009. Our Newsletter will also be switching to a new Editorial Board. We are indebted to the outgoing board members, Drs Kah-lin Choo, James Ho and Maureen Wong, for their great contributions over past many years. We warmly welcome the new members, namely Drs Yuk-lung Kwok, David Lam, Arthur Lau, Man-po Lee, Ms Amon Lam and Ms Mary Tsang. With an expanded team of colleagues from different professions, the Editorial Board will strive to maintain the good work of our predecessors and try to enrich the contents of newsletter to foster communications among members and colleagues. In this issue, we continue to provide comprehensive information and knowledge in various sections as before and have reported the Annual Scientific Meeting of the two Societies that was held successfully last month. I hope you will find the content interesting and useful. Finally, on behalf of the Editorial Board, I would like to thank you all for your continued support.

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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pecial Event

Annual Scientific Meeting 2007

Drs Thomas Mok & Wong Poon Chuen

Chairmen of the ASM Organizing Committee

Similar to previous years, the Annual Scientific Meeting (ASM) co-organized by the Hong Kong Thoracic Society and the American Colleage of Chest Physicians (Hong Kong and Macau Chapter) was successfully held in March again this year.

During the one-day meeting on 11th March, the Organizing Committee had designed a packed and comprehensive programme covering a wide scope of hot and interesting topics in respiratory and critical care medicine, and invited a distinguished panel of local and overseas speakers by whom the lectures were elegantly and informatively delivered.

The ASM began with a Clinical Updates session comprising scientific lectures entitled “Lung Transplantation in Hong Kong: 12 Years’ Experience”, “Pulmonary Aspergillosis” and “Rapid Diagnosis of Drug Resistant Tuberculosis”. These were followed by a session of interesting cases in respiratory medicine, when our doyenne Dr Joseph Pang and Dr Sung-yang So enlightened us with extremely interesting cases of “PacMan” and “A Lady with Pneumothorax” respectively.

Following a lunch symposium on recent advances in the management of obstructive lung diseases, we had an afternoon session about practical tips in respiratory medicine consisting of talks on “Chronic Bronchial Sepsis”, “Weaning Strategies” and “CT Scan Interpretations”. The audience applauded these high-quality talks for their practicality and usefulness to daily patient managements.

After enactment of the amended anti-smoking bill to ban smoking in vast majority of indoor areas this year, many of our fellow colleagues would be playing a pivotal role in helping patients to quit smoking. A tailored workshop on smoking cessation was timely co-organized with the Centre of Health Promotion and the Nursing Studies of the University of Hong Kong to meet the increasing quest for professional knowledge and advice.

The ASM ended with a special symposium on air pollution, which was held in response to the growing concern of worsening of air quality in Hong Kong over recent years.

Medical science is advancing in leaps and bounds. With the closing of this ASM, we look forward to next occasion of sharing and learning among colleagues.

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Council Members of the Hong Kong Thoracic Society, the American College of Chest Physicians (Hong Kong and Macau Chapter) and Hong Kong Lung Foundation

From Left to Right: Prof. PL Ho, Prof. Marc Judson (from USA), Dr CF Wong, Dr PC Wong (chairman) and Dr David Hui (chairman) at the session of Clinical Update

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Prof. WK Lam (chairman) presented the souvenirs to Dr SY So and Dr J Pang after their session of Interesting Case Presentation.

Prof. TH Lam at the “Workshop of Anti-smoking” Dr SS Ho (chairman) presented the souvenir to Dr Sophia Chan after the “Workshop of Anti-smoking”

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From left to right: Dr Clara Ooi, Dr Osburga Chan, Dr Kenneth Tsang, Dr CM Chu (chairman) and Dr KS Chan (chairman) at the session of Practical Tips

Dr WM Chan (chairman) presented souvenirs to speakers of symposium of Air Pollution (from left to right): Mr SW Pang, Prof. Anthony Hedley and Ms Christine Loh

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linical Meeting Summary

Therapeutic Drug Monitoring And Tuberculosis

Dr. WM Leung and Dr. KC Chang

Department of Health

Therapeutic drug monitoring (TDM) is the application of pharmacokinetics and pharmacodynamics to optimise response to drug treatment by maintaining serum drugs levels within a therapeutic range. Examples of drugs for which TDM has been applied in clinical practice include aminoglycosides, vancomycin, cyclosporin, and digoxin. TDM is impossible without reasonably accurate assay techniques that are preferably rapid, convenient, and inexpensive. Ideally, the following conditions should be met before considering TDM. First, there is a reasonable proxy for drug concentration at the site of action. Second, the therapeutic margin is narrow. Third, it is difficult to predict drug level by dosage. Fourth, there exists no clinically observable therapeutic or toxic endpoint. Owing to the above consideration, TDM is not commonly considered in the management of tuberculosis (TB). Experts have recommended TDM for improving treatment in special subgroups of patients with TB1-3, but there are only limited data in support of such recommendations. Previous studies showed a dose-response for rifampicin and pyrazinamide3. US Pubic Health Services TB trial 22 found an association between low plasma isoniazid concentrations and failure/ relapse among patients treated with once-weekly isoniazid and rifapentine4. TDM in obese patients showed that lean body weight was preferable to actual body weight in prescribing anti-TB drugs5. There have been case reports of reduced anti-TB drug levels in patients with human immunodeficiency virus (HIV) infection6,7, which may be related to malabsorption8. Mehta and coworkers reported sub-therapeutic rifampicin levels in six patients with TB and slow response to standard anti-TB treatment despite favourable sensitivity patterns and directly observed treatment9. Given a lack of conclusive evidence on the role of TDM in the management of TB, a case-control study was conducted in the TB and Chest Service to examine the relationship between slow culture conversion and plasma rifampicin levels among a cohort of patients with culture-positive pulmonary TB and slow smear conversion. The cohort was assembled prospectively in government chest clinics. Slow culture conversion and slow smear conversion were defined, respectively by positive sputum culture and the presence of acid-fast bacilli in sputum smears after standard pyrazinamide-containing regimen for at least eight weeks. Patients with multi-drug resistant TB or HIV infection were excluded. A logistic risk model, which compared cases with slow culture conversion and controls with negative sputum culture between 7.5 weeks and 10.5 weeks post-treatment, showed no significant association between slow culture conversion and rifampicin levels with a best-estimated odds ratio close to unity. The role of TDM in the management of slow smear converters therefore remains to be clarified.

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References:

1. Peloquin CA. Using therapeutic drug monitoring to dose the antimycobacterial drugs. Clin Chest Med 1997; 18:79-87.

2. Peloquin CA. Tuberculosis drug serum level. Clin Infect Dis 2001; 33:584-585. 3. Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 2002;

62:2169-2183. 4. Weiner M, Burman W, Vernon A, et al. Low Isoniazid Concentrations and Outcome of

Tuberculosis Treatment with Once-Weekly Isoniazid and Rifapentine. Am J Respir Crit Care Med 2003; 167:1341-1347.

5. Geiseler PJ, Manis RD Jr, Maddux MS. Dosage of antituberculous drugs in obese patients. Am Rev Respir Dis 1985; 131:944-946.

6. Berning SE, Huitt GA, Iseman MD, Peloquin CA. Malabsorption of antituberculosis medications by a patient with AIDS. N Engl J Med 1992; 327:1817-1818.

7. Patel KB, Belmonte R, Crowe HM. Drug malabsorption and resistant tuberculosis in HIV-infected patients. N Engl J Med 1995; 332:336-337.

8. Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection. Ann Intern Med 1997; 127:289-293.

9. Mehta JB, Shantaveerapa H, Byrd RP, Morton SE, Fountain F, Roy TM. Utility of rifampicin blood levels in the treatment and follow-up of active pulmonary tuberculosis in patients who were slow to respond to routine directly observed therapy. Chest 2001; 120:1520-1524.

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linical Meeting Summary

“What Lies Beneath”

Dr. CM Wong, Dr. WK Lam, Dr. Choo Kah Lin and Dr. Wong Kwan Keung

Department of Medicine, North District Hospital

Case History Mr. Liu is an 82-year-old gentleman who presented to our unit in June 2006. He was an ex-smoker and retired soldier. The patient had a spinal cord infarct in 1993 resulting in bilateral spastic paraparesis and neurogenic bladder. He also had hypertension, duodenitis, reflux oesophagitis, hiatus hernia, urethral stricture and history of appendicectomy. He was on long term methyldopa, famotidine, baclofen and gabapentin1 for his medical conditions. He was admitted to our unit on 17th June 2006 and presented with shortness of breath for few days. There was no history of cough, sputum or fever. He also did not have chest pain, orthopnoea or ankle oedema. There was no history of malar rash, discoid rash, photosensitivity, oral ulcer, arthralgia, myalgia, dysphagia or Raynaud’s phenomenon. He had no occupational exposure to silica or asbestos. He did not keep birds or pets. There was no recent travel history or poultry contact. On admission, the blood pressure was 160/70 mmHg and pulse rate was 65 beats per minute. Oxygen saturation was 93 % while the patient was breathing 100 % oxygen via the non-rebreathing mask. The body temperature was 36.5 degree Celsius. On examination, there was bilateral fine basal crepitations on auscultation. There was no cardiac murmur or lower limb oedema. Jugular venous pressure was not elevated. There was no finger clubbing, joint swelling/ deformity, sclerodactyly or skin rash. Other parts of physical examination were unremarkable. Urine dipstix was trace for protein and negative for blood. Baseline blood test results on admission:

Haematology results WCC: 10 (Neu 7.7) x 109/l ↓Hb: 12.5 g/dl (NcNc) PLT: 342 x 109/l PT: 11.2 s APTT 35.4 s INR 1.0

Biochemical results ABG: ↑pH 7.47, pCO2 4.85 kPa, pO2 13.09 kPa, BE 2.2 mmol/l, HCO3 25.8 mmol/l, SaO2 98 % (FiO2 1.0), ↓PaO2: FiO2 ratio: 98.4 mmHg RFT: Na 129, K 4.3, Urea 5.0 mmol/l, Cr 55 µmol/l LFT: Bil 8 ↓Alb 31, Globulin 41 g/dl, ALP 111, ALT 20 U/ml CK 28, ↑LDH 321 U/ml Spot glucose 5.3 mmol/l

1 The listed medications have no known association with drug-induced interstitial pneumonia.

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Chest radiography (CXR) on admission showed bilateral diffuse ground glass opacity and reticulonodular shadowing bilaterally (Fig. 1). Electrocardiogram was normal. Echocardiogram demonstrated normal left ventricular ejection fraction 76.8 % and normal left ventricular size. No other abnormalities were identified.

Fig. 1 CXR on 17/6/06

He was initially managed as severe community acquired pneumonia and given amoxicillin/clavulanate and azithromycin intravenously. Amoxicillin/clavulanate was changed to cefotaxime on day 2 of admission. Patient however remained apyrexic during hospital stay. Sputum grew oral commensals only. The acid fast bacilli smear and culture were negative for three times. Blood culture did not yield any organism. Old chest radiographs in 1999, 2002 and 2004 were traced, showing progressively increased bilateral lower zone reticular shadowing. High resolution computerized tomography (HRCT) of thorax on day 2 of admission showed subpleural fibrosis with honeycombing at bilateral lung bases which was associated traction bronchiectasis. There were ground glass opacities in both lungs and which was predominant in upper zones. There was mild bilateral pleural effusion (Fig. 2).

Fig. 2 HRCT on 18/6/06

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Further blood tests: RF –ve ANA +ve Titre 640 Anti-ENA –ve (Sm –ve , RNP –ve , La –ve , Ro –ve , Jo-1 –ve , Scl-70 –ve ) ANCA +ve, Anti-PR3 normal, Anti-MPO normal VDRL: -ve

Histological diagnosis was not made as the patient refused bronchoscopy and surgical lung biopsy. In view of progressive bilateral lower zone reticular shadowing over the past few years, ground glass opacities with underlying usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis on HRCT thorax, and absence of evidence suggesting infections and connective tissue diseases, the clinical diagnosis at that juncture was acute exacerbation of idiopathic pulmonary fibrosis (IPF).2 The patient was given methylprednisolone 1 g intravenously for 3 consecutive days since day 4 of admission which was then followed by prednisolone 60 mg daily. The patient improved both clinically and radiologically and was transferred to convalescence hospital for rehabilitation on day 10 of admission. Oxygen was eventually weaned off. He was followed up in our outpatient respiratory clinic and prednisolone was tailed down to 10 mg daily together with addition of azathioprine 25 mg daily. Physical examination on follow-up showed the normal power of the upper limbs with no proximal muscle weakness. HRCT thorax at 3 months showed that the ground glass opacities had already resolved with residual subpleural fibrosis and traction bronchiectasis (Fig. 3).

Fig. 3 HRCT on 28/9/06

Discussion Idiopathic pulmonary fibrosis is clearly defined as one of the most common form of idiopathic interstitial pneumonia by international guidelines. It is a distinctive type of chronic fibrosing interstitial pneumonia of unknown cause limited to the lung with histological pattern of UIP. (2) The clinical course of IPF is traditionally believed to be chronic and slowly progressive. However, rapid deterioration during the course of illness can sometimes be observed. Martinez and colleagues demonstrated in IPF patients the change of

2 Pleural effusion had been reported to be a CT feature in 6 % of IPF patients. (1)

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physiological (forced vital capacity, diffusion capacity for carbon monoxide, alveolar-arterial gradient) and functional parameters (Transition Dyspnoea Score and Shortness of Breath Questionnaire) were minimal over a median period of 76 weeks. However, twenty-three percent of them required hospitalization for acute respiratory disorder and 21 % died. Idiopathic pulmonary fibrosis was the major cause of death in 89 % of patients who died, and acute exacerbation of the illness preceded death in 47 % of these patients. (3) Therefore, the disease may be less gradual decline and more a step-like process, with periods of relative stability punctuated by periods of acute decompensation. The disease carried high mortality with median survival from 2 to 4 years.

Kondoh et al has proposed the diagnostic criteria for acute exacerbation of IPF. It included aggravation of dyspnoea within 1 month, hypoxaemia with arterial oxygen tension to inspired oxygen tension ratio of less than 225 mmHg, newly developing pulmonary infiltrates on chest radiography and absence of apparent infection or heart disease. (4) Kim and colleagues showed that the 2-year frequency of acute exacerbation of IPF was 9.6 %. Most of the cases were idiopathic and no significant risk factor was identified. (5) The clinical features included rapidly progressive dyspnoea, cough, scanty sputum, fever, inspiratory crackles and clubbing. (4-6) Laboratory findings were characterized by hypoxaemia (PaO2/FiO2 70-144 mmHg), elevated inflammatory markers (white cell count, erythrocyte sedimentation rate, C-reactive protein), lactate dehydrogenase, fibrinogen, cancer antigen 19-9 and thrombocytopenia. (4-6) High resolution CT thorax may show one of three radiological patterns that included diffuse, multifocal and peripheral pattern. The peripheral pattern was associated with a better prognosis. (5) When bronchoscopy was performed in patient with acute exacerbation of IPF, bronchoalveolar lavage was characterized by marked neutrophilia (11-90 %), raised albumin (139-357 µg/ml) and type II reactive cells. (4, 6) Histology may show various combination of typical UIP and diffuse alveolar damage (DAD) area (DAD:UIP area ratio 3:1-1:1.5) and some of them may have hyaline membranes as well. Other histological features included type II pneumocyte hyperplasia, fibroblastic foci, organizing pneumonia and haemorrhage with capillaritis. (4-6) Acute interstitial pneumonia (Hamman-Rich syndrome) was the one of the important differential diagnosis in this disease entity. It was the most common form of rapidly progressive diffuse interstitial lung disease characterized by DAD on lung biopsy. Distinguishing acute exacerbation of IPF from acute interstitial pneumonia hinges on recognition of underlying UIP in the former. While histology can facilitate the diagnosis of various forms of interstitial lung disease, the safety of surgical lung biopsy has been debated. In Kim’s study, two of the 11 patients with acute exacerbation developed the exacerbation shortly after surgical lung biopsy. (5) The short-term mortality rate (16.7 %) after surgical lung biopsy was higher in patients with IPF, compared with the mortality rate of 1.7 % in 771 unselected patients undergoing surgical lung biopsy at the same institution. (7) Kondoh and colleagues investigated 236 consecutive patients with interstitial pneumonia who underwent surgical lung biopsy. There were 5 patients (2.1 %) (IPF 3; non-specific interstitial pneumonia 1; cryptogenic organizing pneumonia 1) who developed acute exacerbations 1-18 days after surgical lung biopsy. (8) Lettieri and his colleagues had conflicting results concerning the safety of surgical lung biopsy. They found that among patients with IPF, death following surgical lung biopsy was rare and did not differ statistically from the mortality observed in patients with non-IPF interstitial lung disease. (9)

Bronchoalveolar lavage (BAL) had been reported to cause acute exacerbation of IPF. Hiwatari investigated 124 IPF who underwent BAL, three patients (2.4 %) developed acute exacerbation of IPF immediately after the procedure. In contrast, no deteriorations after BAL observed in 282 patients with other pulmonary diseases in

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the same period. Therefore, BAL sometimes induced a progressive deterioration in IPF patients. (10) There was no treatment guideline for acute exacerbation of IPF. Most of the studies included high dose corticosteroids and broad-spectrum antibiotics as the mainstay of treatment though it was not effective most of the time. In Kim’s study, all patients were treated with broad-spectrum antibiotics and high dose corticosteroids. The mortality rate was 81.8 %. (5) Ambrosini et al reviewed 5 patients with acute exacerbation of IPF who all treated with high dose methylprednisolone 500-1000 mg daily for three days and cyclophosphamide. They yielded a similar mortality rate of 80 %. (6) In view of limited effectiveness of corticosteroids and cyclophosphamide, other immunosuppressive agents were investigated. Inase and colleagues examined the effect of cyclosporin A on acute exacerbation of IPF. In their study, all 13 patients received pulse-therapy with methylprednisolone (1000 mg/day for 3 days), followed by oral prednisolone (40-60 mg/day). Seven patients were given additional cyclosporine A (1-2 mg/day). Those treated with cyclosporin A had a trend of better survival rate. (11) Homma et al reported a significantly better survival for those patients with acute exacerbation of IPF received cyclosporin A when compared to historical cohort. (12) In a 3-year prospective and controlled study, Kubo and colleagues investigated the role of anticoagulation on clinical course and mortality of IPF. Treatment group received prednisolone plus warfarin as outpatient. Warfarin was replaced by low-molecular weight heparin if they were hospitalized. Control group received prednisolone alone. Although rate of readmission due to acute exacerbation was similar, treatment group had significantly decreased mortality associated with acute exacerbation (18 %) when compared to control group (71 %). (13) Azuma et al performed a randomized, double-blinded, placebo-controlled study on the use of antifibrotic agent pirfenidone in IPF. Acute exacerbations occurred in 5 (14 %) out of 35 patients in placebo group but in none of the 72 patients receiving pirfenidone during follow-up. The trial was aborted early at 6 months by the data safety and monitoring board because of this finding despite this is only a secondary end-point of the study. (14) Therefore the promise of an effective therapy for IPF exacerbations may holds in preventing their occurrence rather than treatment of acute episodes.

Although IPF is considered to be a chronic and progressive disease, it must be noted that some patients with IPF experienced acute exacerbation during their clinical course, and our case was not exceptional. Further studies are required to answer the underlying pathogenesis as well as the effective therapeutic approach for this disease entity.

References:

1. Lim MK, Im JG, Ahn JM, et al. Idiopathic pulmonary fibrosis vs. pulmonary involvement of collagen vascular disease: HRCT findings. J Korean Med Sci 1997; 12:492-498

2. American Thoracic Society, European Thoracic 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

3. Martinez FJ, Safrin S, Weycker D, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 2005; 142:963-967

4. Kondoh Y, Taniguchi H, Kawabata Y, et al. Acute exacerbation in idiopathic

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pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest 1993; 103:1808-1812

5. Kim DS, Park JH, Park BK, et al. Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J 2006; 27:143-150

6. Ambrosini V, Cancellieri A, Chilosi M, et al. Acute exacerbation of idiopathic pulmonary fibrosis: report of a series. Eur Respir J 2003; 22:821-826

7. Allen MS, Deschamps C, Jones DM, et al. Video-assisted thoracic surgical procedures: the Mayo experience. Mayo Clin Proc 1996; 71:351-359

8. Kondoh Y, Taniguchi H, Kitaichi M, et al. Acute exacerbation of interstitial pneumonia following surgical lung biopsy. Respir Med 2006; 100:1753-1759

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

10. Hiwatari N, Shimura S, Takishima T, et al. Bronchoalveolar lavage as a possible cause of acute exacerbation in idiopathic pulmonary fibrosis patients. Tohoku J Exp Med. 1994; 174:379-386

11. Inase N, Sawada M, Ohtani Y, et al. Cyclosporin A followed by the treatment of acute exacerbation of idiopathic pulmonary fibrosis with corticosteroid. Intern Med 2003; 42:565-70

12. Homma S, Sakamoto S, Kawabata M, et al. Cyclosporin treatment in steroid-resistant and acutely exacerbated interstitial pneumonia. Intern Med 2005; 44:1144-50

13. Kubo H, Nakayama K, Yanai M, et al. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 2005; 128:1475-1482

14. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005; 171:1040-1047

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pecial Event

Asthma Symposium

Dr. Thomas Mok1 and Dr. PC Wong2

1. President of the Hong Kong Thoracic Society

2. President of the American College of Chest Physicians (HK & Macau) Chapter

With the release of revised GINA guideline in late 2006, much attention has returned to a better management of asthma. The Hong Kong Thoracic Society and American College of Chest Physicians (Hong Kong and Macau Chapter) have timely arranged a special symposium to refresh and update colleagues about knowledge in this area. The symposium was held on 6 March 2007 at Conrad Hotel. Our audience was very privileged to have two distinguished speakers delivering informative and enlightening talks in that evening. The first talk on “Pathogenesis and treatment of asthma exacerbations” was given by Prof Sebastian Johnston from UK. It was immediately followed by our local expert, Dr Christopher Lai, with a talk on “An update on the GINA guideline and management of chronic asthma”. The symposium ended with a “Q & A” section between the two experts and the audience.

Dr Christopher Lai and Prof Sebastian Johnston on the stage

Dr Wong Poon-chuen presented souvenirs to two guest speakers

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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: soky@ha.org.hk Questions for the next issue:

1. Management of malignant pleural effusion (from Dr.David CL Lam, Queen Mary Hospital)

2. What are the alternative treatments available to PCP if a

patient cannot tolerate co-trimoxazole? (from Dr. Man-po Lee, Queen Elizabeth Hospital) 3. Preparation of patients for home invasive ventilation

(from Miss Amon YP Lam, Pamela Youde Nethersole Eastern Hospital)

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ractical Corner

What are the physiologic changes involved in high altitude? Dr. Angus HY Lo Department of Medicine, Pamela Youde Nethersole Eastern Hospital

With the advance of modern transportation, increasing number of HK people are expected to travel to highlands for recreation and adventure. Taking the newly inaugurated Qingzang railway as an example, passengers will be brought through heights up to 5,072 m above sea level in Tanggula Pass during its course from Xining to Lhasa. Larger and larger number of our patients and our friends will be exposed to high altitude as a result. It is, thus, important for all of us to be familiar with the physiological changes involved in high altitude. Owing to the limitation of the scope of present article, our discussion will be focused on changes in ventilation and some important organ systems. With increasing altitude, the barometric presure falls but the fractional concentration of oxygen in the air (ie FiO2), and the saturated vapour pressure of water at body temperature (which equals 47mmHg) remain constant. The PO2 of inspired gas is therefore reduced in high altitude as follows,

Inspired gas PO2 = 0.21 x (Barometric pressure – 47) mmHg E.g. At sea level, PO2 = 0.21 x (760 – 47) = 149 mmHg.

While in 4880m, PO2 = 0.21 x ( 412 – 47) = 76 mmHg

A. Ventilatory changes can be divided into 3 phases: 1) Acute hypoxic response (AHR) Upon acute ascent to high altitude, the PO2 drops as calculated above. Chemoreceptor activity of carotid body increases almost immediately. This leads to a nearly immediate acute increase in ventilation, which continues to rise for around 5-10 minutes, rapidly reaching a high level. This can be seen as a fall in PCO2 within the initial few minutes after hypoxic exposure in Fig 1. 2) Hypoxic ventilatory decline (HVD) Shortly after onset of the acute hypoxic response, minute ventilation reaches a peak and begins to decline. This decline is initially related to the respiratory alkalosis and drop in PCO2 due to the acute hypoxic response itself. However, beginning a few minutes after the onset of AHR, and lasting for up to 20-30 minutes, an additional mechanism not explained by hypocapnia begins to operate that reduce minute ventilation to a lowered level of hyperventilation. This unknown mechanism is known as hypoxic ventilatory decline (HVD) or “roll off”. HVD is responsible for the significant fall in arterial PO2 due to reduced ventilation and results in many of the symptoms seen during the first few hours and days at altitude. This can be visualised as a rise in PCO2 after its initial fall in the first 15 minutes in Fig 1.

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hypoxia in Fig 1.

AHR HVD

Fig 1 Effect of prolonged hypoxia on ventilation

3) Ventilatory response to sustained hypoxia When hypoxia continues, a second and slower rise in ventilation occurs. Such rise may lasts for days to weeks at high altitude. This is the ventilatory change seen in acclimatisation. Classically, renal compensation for the respiratory alkalosis to allow for full translation of hypoxia into hyperventilation has been offered as the explanation for this gradual increase in ventilation. Subsequent data revealed that blood pH hardly changes despite prolonged hypoxia. Mechanisms involving CSF pH, or Brain pH have been proposed to explained this persistent rise in ventilation. However, increased sensitivity of central and peripheral chemoreceptors (especially carotid body) to hypoxia seems more important behind this progressive hyperventilation. For most people, full acclimatisation occur within 1 week. B. Cardiovascular and pulmonary vascular changes Apart from hyperventilation, cardiac output also increases with altitude. This is brought on chiefly by an increase in heart rate. The cardiac output then reduces after first few days with reduction in both the stroke volume (due to reduced plasma volume and hence preload) and heart rate. Concerning the pulmonary vascular changes, hypoxia induces pulmonary vasocnstriction. This results in pulmonary hypertension and tend to improve the V/Q matching up to an altitude of 4550m. In contrast, excessive vaocontriction in certain individuals worsen V/Q balance and may even results in regional hyperperfusion followed by stress failure in capillaries and pulmonary edema. In the long run, such changes may also results in excessive pulmonary hypertension and right heart failure C. Hematologic changes With hypoxia, erythropoeitin level increases within 24-48 hrs. Its mean level being proproportional to the altitude attained. On average, its level falls within 3 weeks as acclimatization progresses. Both red cell volume and total blood volume increases. Together with a fall in plasma volume due to diuresis, the hemoglobin concentration incresaes. The changes increase oxygen content and delivery at high altitude. However, when hematocrit approaches 60%, viscosity incresaes and first cardiac output and then oxygen delivery may actually fall. Further physiologic changes occur in various aspects of our body including: changes in oxygen affinity, CNS response, cellular and tissue adaptation, fluid hemostasis as well as changes in sleep pattern is beyond the scope of this article. Interested readers are referred to the references listed below for a more comprehensive review of the subject.

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References: 1. Andrew Lumb. Nunn’s Applied Respiratory Physiology. 6th ed. Italy: Elsevier, 2005; 17: 254-266 2. John Murray, Jay Nadel. Textbook of Respiratory medicine. 3rd ed. Philadelphia: W.B. Saunders,

2000; 70: 1915-50 3. West JB, Hackett PH, Maret KH, et al. Pulmonary gas exchange on the summit of Mount Everest. J

Appl Physiol 1983; 55: 678-87 4. Bisgard GE, Forster HV. Ventilatory responses to acute and chronic hypoxia. In: Fregly MJ, Blatteis

CM, eds. Handbook of physiology – section 4: Environmental physiology. New York: Oxford University Press, 1996.

5. Houston CS, Sutton JR, Cymerman A, et al. Operation Everest II: man at extreme altitude. J Appl Physiol 1987; 63: 877-82.

20

ractical Corner

What is tracheobronchomalacia? Dr. Sai-On Ling Department of Medicine, Kowloon Hospital

Introduction Tracheobronchomalacia (TBM) is a form of dynamic central airway obstruction that may mimic asthma and COPD. The term is often used interchangeably with excessive dynamic airway collapse (EDAC). It is thought to be an underdiagnosed condition.

Definitions Tracheobronchomalacia, tracheomalacia and bronchomalacia The term malacia originates from the Greek word 'malakia', meaning softness. Tracheobronchomalacia (TBM) is defined as a condition in which there is weakness of the tracheobronchial cartilaginous structures due to softening of the supporting cartilage and hypotonia of the myoelastic elements such that the airway is more susceptible to collapse.When the trachea alone is involved, the condition is referred to as tracheomalacia (TM), which may be localized or may involve the whole trachea. When there is isolated weakness and easy collapsibility of one or both mainstem bronchi without tracheal involvement, the term bronchomalacia is used. This condition is much less common than TM and TBM. Excessive dynamic airway collapse Normally, the compliant intrathoracic trachea and bronchi dilate with inspiration and narrow with expiration (due to invagination of the posterior membrane of the tracheobronchial tree), as a result of the difference between intrathoracic and intraluminal pressures. A certain degree of dynamic airway collapse (DAC) is physiological in normal individuals, facilitating expectoration and secretion clearance. A reduction of airway lumen by 50% or more in the sagittal diameter, however, has been considered abnormal. DAC is exaggerated in TBM. It is also accentuated in some patients with chronic bronchitis, emphysema, asthma, or the condition may occur as an isolated finding. Strictly speaking, the term EDAC should be used when the exaggerated DAC is due to invagination of the posterior membrane alone without weakness of the cartilaginous structures. Morphologies of TBM

When there is weakness of the anterior cartilaginous wall of the airway, the airway lumen will assume a crescent appearance (scabbard shape). When the lateral wall is involved, the airway lumen will assume a saber-sheath appearance (fissure shape). A combined or circumferential type refers to a combination of the

21

crescent and saber-sheath types, or when there is circumferential narrowing of the airway lumen in diseases such as relapsing polychondritis. Aetiology The primary form of TBM is congenital and is mainly a disease of infancy. Acquired forms of TBM and EDAC are disorders of middle aged and elderly people. They can be idiopathic or secondary to other causes. Indwelling tracheotomy and endotracheal intubation with inflatable cuffs are the commonest causes of the acquired forms. The mechanisms of injury include pressure necrosis, impaired blood supply, infection and friction of tubes on the airway mucosa. The malacic area is focal and may occur at the site of the inflatable cuff, at (or 1.5cm below) the tracheostomy stoma, or at the point of impingement of the tip of the tracheostomy or endotracheal tube (ETT) on the tracheal wall. Risk factors include recurrent intubation, prolonged duration of intubation and the use of high-dose steroids. Other secondary causes include closed chest trauma (such as steering wheel injuries with resultant tracheal fractures), chronic inflammation and irritation from smoking or air pollution, chronic airway and soft tissue inflammation in relapsing polychondritis, malignancy especially lung and thyroid cancers (most commonly after thyroidectomy), mechanical anatomic factors as seen after pulmonary resections (the postpneumonectomy syndrome) or after lung or heart–lung transplantation, chronic infections such as tuberculosis, chronic compression of the tracheobronchial tree in substernal goiters, mediastinal tumours or vascular anomalies (including double aortic arch, right aortic arch with an aberrant left subclavian artery and ligamentum arteriosum), congenital diseases (including Mounier–Kuhn syndrome and Ehlers–Danlos syndrome), COPD and asthma (associated with EDAC). Clinical Features The symptoms are non-specific and include dyspnoea, difficulty clearing secretions, recurrent bronchitis or pneumonia, cough and syncope during episodes of coughing. The cough is described as seal-like barking and is due to expiratory collapse and vibration of the floppy membranous wall against the anterior airway wall. Actually, TBM or EDAC may be one of the commonest causes of chronic cough in non-smokers. Haemoptysis may also occur. Physical examination may reveal rhonchi or decreased breath sounds. Progressive hypercapnic respiratory failure requiring mechanical ventilation has also been reported. The condition may be masked during mechanical ventilation because the ETT partially stents the trachea and positive-pressure ventilatory support acts as a pneumatic stent, keeping the airway lumen open. Once the positive pressure or the ETT is removed, the patient may go into respiratory distress and require reintubation. Consequently, unexplained extubation failure should prompt evaluation for TBM.

Diagnostic Tests Pulmonary Function Tests Pulmonary function tests may show diminished expiratory flow, typical notching on the flow-volume (FV) loop, dynamic airway compression (calculated as slow vital capacity minus FVC), a biphasic FV loop or flow oscillations. These findings are, however, neither sensitive nor specific.

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Radiology Imaging Studies Traditional imaging techniques such as CXRs or single slice CT scanning are not helpful in diagnosing TBM or EDAC because they are performed during end-inspiration.

Cine fluoroscopy was used in the past to identify TBM. This has been replaced by newer CT techniques, such as Rapid Electron Beam CT and multislice helical CT, which permit volumetric acquisition of data at both end-inspiration and during dynamic expiration. Many investigators employ 50% or more reduction in airway caliber between inspiration and expiration to diagnose TBM. Sagittal images obtained by multiplanar CT scan reformations are helpful for displaying the craniocaudal extent of the disease. The results from CT imaging correlate well with bronchoscopic findings. Nevertheless, paired inspiratory-dynamic expiratory multislice helical CT doubles the radiation dose compared with single-phase acquisition. So a low dose technique for the dynamic portion of the study has been suggested, with comparable accuracy. Dual-phase virtual bronchoscopy images provide an important complement to axial CT scan images for airways that course obliquely such as the mainstem bronchi. Virtual bronchoscopy may obviate the need for conventional bronchoscopy in patients who have contraindications to the latter procedure.

Cine magnetic resonance imaging is also highly sensitive for the diagnosis of TBM. It has the advantage of permitting repeated assessments during multiple respiratory maneuvers due to its lack of ionizing radiation. Future studies comparing CT scanning, MRI and conventional bronchoscopy are necessary to define their roles. Bronchoscopy Today, bronchoscopic visualization of dynamic tracheal or bronchial collapse remains the reference or "gold standard" for diagnosing TBM. Both rigid and flexible bronchoscopy can be employed, but the latter is preferred because the patient can breathe spontaneously and follow commands to perform deep breathing, forced exhalation and cough maneuvers to elicit the collapsibility of the airways. There is no standard method to quantify the severity of the airway collapse. Some classify the condition as mild if the obstruction during expiration is to one half of the lumen, moderate if it reaches three quarters of the lumen, and severe if the posterior wall touches the anterior wall. Quantitative or morphometric bronchoscopy has been proposed to directly quantify the degree of airway collapse. The bronchoscopic findings during inspiration, passive expiration and active expiration are recorded with a video camera attached to the bronchoscope. Selected images are morphometrically analysed for maximal cross-sectional area (CSA) during inspiration and minimal CSA during passive and active expiration and the expiratory airway collapse can be calculated (inspiratory CSA − expiratory CSA)/inspiratory CSA × 100%).

Treatment

The treatment modality depends on the severity of symptoms, the degree and extent of airway collapse as well as the aetiology. In asymptomatic patients, no treatment is needed. If the patient is symptomatic, treatment is initially supportive

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unless the situation is emergent or progressively worsening, in which cases more invasive options should be considered.

Medical Management

Smoking should be quitted. Any underlying condition should be treated if possible. For example, patients with RP should be treated with steroids or other immunosuppressive agents and the response is usually good. Any associated asthma or COPD should be optimally controlled because the large pressure swings in the thorax caused by bronchospasm may worsen the severity of collapse of the malacic segment. Paradoxically, there may be a dramatic fall in peak flow in response to bronchodilators (reported in paediatric TBM) because the tracheobronchial wall stiffness may further decrease with smooth muscle relaxation after the administration of bronchodilators.

NIPPV NIPPV can be employed to maintain airway patency, facilitate secretion drainage and improve expiratory flow. CPAP acts as a pneumatic stent and reduces expiratory airflow obstruction. It also decreases the elevated inspiratory transpulmonary pressures needed to initiate airflow, thereby reducing the work of breathing. It is likely that nocturnal and intermittent daytime nasal CPAP benefit patients with TBM or EDAC especially in less severe cases, or it may be used as an adjunctive therapy in more severe cases. Large controlled studies are needed to address these issues.

Minimally Invasive Surgery

a) Stents

Airway stents are useful to maintain airway patency in patients with any form of central airway obstruction. More than one stent may be required if the symptoms persist after stenting due to the distal migration of the choke point (flow-limiting segment).

The studded Dumon-type silicone stent is the most commonly used stent. It is easily inserted, repositioned and removed, though rigid bronchoscopy and general anesthesia are required. However, it has the disadvantages of easy collapsibility from extrinsic compression and easy migration.

Metal stents have the advantages that they are not only easily placed by flexible bronchoscopy but also visible on plain radiographs. In addition, they expand dynamically and preserve mucociliary function if uncovered. Moreover, they are less likely to migrate or to cause obstruction by mucus plugging. However, they have the following drawbacks. Firstly, they are difficult to be removed. Secondly, they tend to become epithelialized in the airway, leading to recurrent stenosis. Thirdly, they have the propensity to fracture. These disadvantages render them not a first choice for patients with TBM.If the patient’s symptoms fail to improve with stent insertion, the stent should be removed to avoid complications. If the patient improves but refuses surgery, long-term stenting may be considered.

b) Tracheostomy

Tracheostomy may stent the malacic airway, provides invasive ventilatory support when necessary and offers a secured airway in cases of acute airway obstruction. The tracheostomy tube alone may be effective if it bypasses the focal

24

malacic segment. However, it may be complicated by secondary tracheomalacia and stenosis at the stoma site. Furthermore, it may exacerbate diffuse malacia or EDAC because it bypasses the physiological function of the glottis to maintain a positive transmural pressure that keeps the airway lumen open. Hence, it should not be considered as a first line treatment. Open Surgery

Surgery should be considered for functionally disabling TBM or EDAC that fails other measures, if expertise is available. The insertion of an easily removable stent may be used to identify those patients who are likely to benefit from surgery in the long term.

A number of surgical procedures have been described. These include tracheal resection (for focal tracheomalacia) and various airway splinting techniques: spanplasty to reinforce the membranous portion of the trachea; fixation of the cartilaginous portion of the trachea using a Marlex mesh; tying the posterior wall of the trachea with bone chips, fascia grafts or plastic prostheses; performing autologous costal cartilage grafts to support the tracheal wall; suturing the trachea to dura mater grafts; tracheal implantation of biocompatible ceramic rings and surgical placement of external tracheal stents.

References:

1. Carden KA, Boiselle PM, Waltz DA, Ernst A. Tracheomalacia and tracheobronchomalacia in children and adults: an in-depth review. Chest 2005; 127: 984–1005.

2. Septimiu D. Murgu and Henri G. Colt. Tracheobronchomalacia and excessive dynamic airway collapse. Respirology 2006; 11: 388–406

25

ractical Corner

What environmental hazards are present for the air travellers with respiratory problems, and what are the possible measures? Dr Henry KH Kwok, Hospital Authority Head Office

There are many health hazards that one could face during air travel. Professional travelers, particularly the aircrew members and the business travelers, will be more exposed to such hazards, but the less frequent travelers will not be exempted from such risk, even though the risk of such exposure would be relatively smaller. Here are some of the more frequently encountered risks among travelers. It should be noted that this list is not meant to be exhaustive, and readers are encouraged to consult the relevant publications for more specific types of conditions and hazards.

I) Physical hazards

There are many physical hazards present during air traveling1. Air pressure: commercial aircrafts are usually pressurized to about 8000 ft cabin altitude, which is a significantly lower pressure than that at ground level. This could pose a problem for passengers with entrapped volume of air in body cavities. The typical and best known examples are those with undrained pneumothorax, but it is not uncommon to see passengers having a URI and blocked nasal sinuses to have difficulties in equalizing the middle ear and nasal sinuses pressures, resulting in significant sinus pain and even rupture of ear drums. Other patients at risk include those with intestinal obstructions, recent eye surgeries, recent neurosurgeries, and even dental caries.

Oxygenation: atmospheric oxygen content falls with altitude and could pose a problem as passengers are breathing ambient air. The SpO2 could be as low as 92% for the normal individual at this cabin altitude pressure level, and the SpO2 level could be even lower for those with respiratory diseases, necessitating the need for oxygen therapy during flight. Even pressurized at 8000ft cabin altitude, there is a 25 per cent reduction in the partial pressure of oxygen in the atmosphere associated with ascent, which can result in a detectable impairment in some aspects of mental performance. In the event of sudden depressurization or decompression (eg cabin door accidentally opened during flight at 30000ft), the consequence rapid decompression can reduce the partial pressure of oxygen within the lungs to about 10% of its sea-level value, the corresponding alveolar oxygen tension less than 30mmHg, leading to unconsciousness within 12-15 seconds, and death in minutes.

Low humidity: the relative humidity in the cabin environment is significantly reduced during flight at cruising altitude, and can be as low as 15-20% relative humidity. This can lead to significant dehydration and is further aggravated by

26

diuretic agents like caffeine and alcohol. The resulting dehydration could lead to mucosal dryness and respiratory irritations for the sensitive individuals. Temperature: at cruising altitude the temperature outside the aircraft can be less than -40oC. The cabin air is usually warmed by the air passing through the aircraft jet engine, and the temperature should be ambient for most aircrafts. Nevertheless the fluctuating air temperature could theoretically be a problem for the sensitive airways.

Radiation: air-travelers are not as well shielded from cosmic radiation as people at ground. The higher altitudes that the aircraft is cruising, the larger are the air passengers exposed to cosmic radiation. The radiation dose will also vary with the route of air travel. For example, flying from London to New York will impose a larger dose than flying from London to Rio de Janeiro. This could pose a larger problem of radiation exposure to the professional aircrew members as well as the very frequent air-travelers. Having said that, researches so far have not shown any significant health effects for either passengers or crew.

II) Chemical Hazards

There are many chemical hazards from air traveling relating to indoor air qualities problems inside the aircraft cabinets, some of which are as follows: Environmental tobacco smoke: although mostly banned in airflights, smoking is still permitted by some airlines.

Engine exhaust: this could be a problem before take off and during aircraft taxiing after landing, when the engine exhaust could leak into the cabinet environment.

Volatile organic compounds: such as those emitted from the use of perfumes from the neighboring air-travelers might cause respiratory irritations and asthma like symptoms.

Use of disinfection with pyrethrins and other chemicals: these chemicals might be used for disinfection procedure of the cabin environment after international flights. Any such compounds remaining inside the cabin could be a possible trigger of airway irritations, set aside other consequences of exposure to such compounds.

III) Biological Hazards

Aircrafts could act as a vector for transmissible diseases such as tuberculosis, malaria, and SARS. Tuberculosis: there have been 6 case reports of possible tuberculosis transmissions during air traveling1. In these six instances, a passenger or a member of a flight crew traveled on commercial airplanes while infectious with tuberculosis. In two of the instances, the Center of Disease Control and Prevention concluded that tuberculosis was probably transmitted to others on the airplane. The findings suggested that the risk of tuberculosis transmission from an

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infectious person to others on an airplane was greater on long flights (8 hours or more). The risk of exposure to tuberculosis was higher for passengers and flight crew members sitting or working near an infectious person because they might inhale droplets containing M. tuberculosis bacteria. SARS: another notable disease that has caused widespread panic worldwide. SARS has spread around the world along the routes of international air travel, with outbreaks concentrated in transportation hubs or densely populated areas. The risk might possibly be higher in cases when passengers are not aware that they have been carrying a potentially contagious disease, and thus will impose the chance of dispersing the infectious agent unnoticed. The transmission is no different from any other situation where people are close to each other on other ground level situations. However, the ventilation rates inside an aircraft could be as high as 20-30 air change per hour. Although most aircrafts have air recirculation systems which recycle up to 50% of cabin air, the recirculated air is usually passed through high efficiency particulate air (HEPA) filters, therefore decreasing the chance of any contagious agents circulating inside the cabin.

IV) Ergonomic hazards

The need for prolonged sitting and relative immobility inside an aircraft can pose possible hazards to the passengers. These situations favor the development of venous status in the dependent parts of the body. (Strictly speaking this does not constitute ergonomic hazards which deal with interaction between men and machines, but just hazards that results from the passenger and his/her chair and environment in the cabin). Together with the possible dehydration discussed in previous paragraphs, the formation of deep vein thrombosis (DVT) could be enhanced. However, whether air traveling is associated with development of DVT (particularly among the economy class passengers, and thus the name “Economy Class Syndrome”) is a subject of debate. In one study2, the incidence of DVT among air travelers was estimated to be about 1% among the 1000 studied cohort, while in another study3, the incidence of asymptomatic DVT was as high as 10%.

V) Other issues

There are other issues which could pose certain degrees of problems for the frequent travelers. These include jet lag and other psychological issues like fear of flying and air rage, the latter two of which will not be further discussed here. Jet lag is the term used for the symptoms caused by the disruption of the body’s internal clock and the approximate 24 hour cycle it controls. While jet lag cannot be prevented, it could lead to significant symptoms including malaise, indigestion, and daytime sleepliness. General measures to reduce the effects of jet lag will include the earliest adaptation of the body’s internal clock to the destination time, and plentiful of sleep rest. Various dietary manoeveurs as well as medications like melantonin and sleeping pills have been widely used by travelers, but with varying degrees of success. Melatonin and sleeping pills are generally not recommended for sleep induction or time zone adjustment.

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Preventive measures

Most of the preventive measures for general aviation hygiene for passengers apply for the prevention of air travel hazards. A general health check for all passengers would be advisable in all circumstances. For travelers with a fever, it is definitely not advisable for him/her to travel until the fever has resolved. This is particularly true if he/she has acute URI symptoms with possible compromise in performing the Valsalva maneuver to “clear the ears” by opening the Eustachian tube. The Valsalva maneuver might be mentioned to the passengers, but most passengers unconsciously know about this technique by swallowing or eating (eg a piece of candy offered by the aircrew before takeoff or landing). It is of course important to keep oneself adequately hydrated, bearing in mind the extremely low humidity in the cabin environment. Caffeine intake should only be modest, and alcohol intake should be discouraged altogether. For those with respiratory diseases, it is advisable (although not many patients do this) to consult a doctor – a pulmonologist, occupational physician, travel medicine specialist or aviation medicine specialist likewise—about fitness to fly before the scheduled flight. A minimum of 1-2 weeks before flying should be advocated to optimize the conditions of patients before flying, as well as to allow time for special equipment to be installed on the flight deck. If a patient needs oxygen therapy during flight, the attending physician may need to fill in a MEDA form (also known as Medical Clearance Form) to the airline company for appropriate actions and arrangememt. However, the provision of the MEDA form is not mandatory and varies with legislation differences of different countries

References:

1. Rainford and Gradwell (2006). Ernsting’s Aviation Medicine 4th ed. Hodder Arnold Press. 2. Center of Disease Control and Prevention. Travelers’ Health: Yellow Book. Available at

http://www2.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=tb.htm 3. Hughes RJ, Hopkins RJ, Hill S et al (2003). Frequency of venous thromboembolism in low to

moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet 362(9401): 2039-44

4. Scurr JH, Machin STm Bailey-King S et al (2001). Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial. Lancet 357(9267): 1485-9

29

edcial Statistics Corner

Medical Biostatistics

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

Survival Analysis Survival analysis refers to the special analytic tools for handling data with outcome of interest being either 1. the length of time elapses before occurrence of an event , or 2. the proportion of an event occurring within a serial intervals of time These events usually carry prognostic values in the disease course, and the most commonly studied outcome of survival include: 1. the time to death 2. the time to occurrence of a complication 3. the time to disease relapse Imagine that we follow up a cohort of patients in a 2-year study, where the subjects are observed from the time of diagnosis of a disease to the time of death. Different patients are recruited at different calendar time and there are only 3 possible outcomes to end up with. Which could be death, or lost to follow up, or alive . In the end of the study, each patient will have his/her own survival time recorded. (Fig. 1)

As death may not have occurred for each participant, if we want to estimate the average time to death of the disease, then time information of the survivors and the lost- to- follow up will be censored, because their data is incomplete for use. Under such circumstances, survival analysis allows us to cope with the censored values properly by making full use of all available data. The strategy is that, at any time point, the information of the remaining “ survivors” can function as the

Figure 1

30

denominator, thereby assisting in the calculation of the proportion of death, or conversely, the proportion of survival across various time points. The actuarial life table and the Kaplan- Meier method are the most commonly used survival analysis, their use and method for the statistical comparisons will be discussed in this chapter.

1. Life Table Analysis The Actuarial Life Table Method This method is used to calculate the survival rates of patients during fixed intervals eg years. The following example illustrates the breakdown of various parameters in the setup of a life table. In each year or fixed time interval, the proportion of survivors is independently calculated. Besides, it is assumed that those who were lost to follow-up during the interval were observed for only half of the interval within which they were found lost. The ultimate cumulative proportion of survival in the 5th year for this group of patients is the product of the independent proportion of survival in each of the 5 years. (Table 1)

Finally, we can construct the survival curve by plotting the cumulative survival proportion against the year of follow up. (Fig. 2)

Table 1

Figure 2

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The Kaplan-Meier Life Table Method This method is different from the actuarial method. Instead of calculating the proportion of survival in fixed intervals, the calculation is done only when death occurs, and that the interval could be highly variable. Before the occurrence of next death, all subjects have the same survival rate during that period. A death produces an instantaneous drop in the proportion of survival. Figure 3 shows an example of the how a Kaplan –Meier is constructed. Losses to follow-up and censored patients are removed from the study group after the between-death interval in which they occur. The actuarial method is useful for handling large numbers of survival data, whereas the Kaplan-Meier is particularly good for small sample size study.

Figure 3

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2) Test of Significance for Survival Analysis Survival curves can be compared and have their observed difference be tested for statistical significance. In fact, the development of powerful statistical modeling technique now allows adjustment of various confounding factors in a set of survival data.

Significance tests for proportions Survival curves derived from actuarial life table method can be compared with the use of z tests , for the difference in proportion of survival between groups.

Logrank Test Kaplan-Meier survival curves are tested with logrank test. This is essentially a chi-square test that compares the probability of survival between the 2 groups everytime a death occurs.

Cox Proportional Hazard Models This is a kind of multiple logistic regression used to control for various confounding variables in a survival analysis. In reality, survival data from different groups of patients are influenced by many covariates other than the disease or intervention given. With the statistical modeling, the impact of these covariates on survival times can also be evaluated.

References: 1. Epidemiology in Medicine. Hennekens, Burring Little ,Brown 2. Epidemiology, Biostatistics and Preventive Medicine. James F. Jekel, Joann G. Elmore, David L.

Katz W.B. Saunders 3. Statistical Methods in Medical Research. P. Armitage & G. Berry. Third Edition. Blackwell Science. 4. Epidemiology. Leon Gordis. Second Edition. Saunders

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Name of the book: AACN Protocols for Practice: Noninvasive Monitoring 2nd Edition Publisher: Jones and Bartlett Publication year: 2006 Editors: Suzanne M. Burns ISBN 9780763738259 T

ook Review Column

his book is evidence-based practice resources for use by clinicians, educators, and researchers. Each series of protocols

makes recommendations for the application, practice, and monitoring associated with a device, procedure, or practice.

These protocols are designed to promote evidence-based practice by providing the latest patient care research findings in a format that is easy to understand and integrate into clinical practice. The protocols can be used to guide care in a variety of clinical situations in acute care, progressive care, or even in the home. Each protocol is introduced by a case study, which is followed by general information about the technology, occupational hazards, ethics considerations, competency issues, and practice recommendations. Recommendations are rated according to the level of evidence that is available to support the statement. Annotated bibliographies, suggested readings, and cross references provide guidance for learning more about the specific device or patient care system

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

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

22-25 June 2007 World Asthma Meeting 2007 Istabbul, Turkey

World Asthma Meeting 2007 Committee Info: www.wam2007.org

2-5 August, 2007 Kuala Lumpur Malaysia

1st Asia Pacific Region Conference – International Union Against Tuberculosis & Lung Disease Info: www.tibi2007.com Email: tibi2007@console.com.my

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

15-17 September, 2007 Stockholm Sweden

17th ERS Annual Congress Info: http://www.ersnet.org/ers/default.aspx?id=3924 Email: staff@stofair.se

20-25 October, 2007 Chicago, Illinois U.S.A

CHEST 2006 Info: www.chestnet.org/CHEST

30 November – 4 December, 2007 Gold Coast Australia

12th Congress of the APSR Info: http://www.apsresp.org/congress/2007.html

2-6 December, 2007 Bangkok Thailand

World Allergy Congress 2007 Info: http://www.congrex.com/wac2007/start.asp E mail: info@worldallergy.org

28 -30January, 2008 Florida USA

44th Annual Meeting of The Society of Thoracic Surgeons Info: www.sts.org Email: sts@sba.com

14-18 March, 2008 Philadelphia, USA

64th Annual AAAAI Meeting Info: http://www.aaaai.org/members/meetings/future_meetings.stm

28 Mar- 2 Apr, 2008 Melbourne Australia

TSANZ ASM Info: www.thoracic.org.au

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orthcoming Clinical Meetings

Date Hosting Hospital/Centre

May 10, 2007 Clinical meeting by Pamela Youde Nethersole Eastern Hospital and Ruttonjee Hospital

Venue: Lecture Theatre: Ruttonjee Hospital

Time: 6:30pm

July 19, 2007 Clinical meeting by Wong Tai Sin Hospital and Kwong Wah Hospital

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 11 March 2007, there are 753 Members (201 Ordinary members, 5 Honorary members, 73 Life members and 474 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 CY Tam, Department of Medicine, Tuen Mun Hospital) and send the letter with a cheque of HK$2,000 to Dr Loletta So, Department of Medicine, Pamela Youde Nethersole Eastern Hospital. 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 (soky@ha.org.hk) 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