Tentative scientific programme

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Once again, the APSR will be at the ERS International Congress, this time at IFEMA Feria de Madrid, 15:00–15:30 on 29 September, with the following (tentative) programme:

Further details of the World Village here

We are pleased to announce that the paper entitled Three-dimensional photography for the evaluation of facial profiles in obstructive sleep apnoea has been selected for the 2019 Fukuchi Award for the best original research paper published in Respirology Vol 23.

From left to right: Ning-Hung Chen (author), Yu-Chen Huang (study team member), Kate Sutherland (author), Yu-Sheng Lin (study team member), Hung-Yu Huang (study team member), Li-Pang Chuang (author).

The award will be formally presented at the next APSR Congress in Hanoi, Vietnam. The Senior Author on the paper, Dr Ning-Hung Chen, will attend the Award ceremony to accept the award on behalf of the authors.

Summary
Craniofacial structure is an important determinant of obstructive sleep apnoea (OSA) syndrome risk. Rapid quantitative analysis of facial surface morphology is needed for large population-based studies. Radiation-free three-dimensional stereo-photogrammetry provides accurate craniofacial measurements in patients with OSA which are highly concordant with those obtained by computed tomography.

Continuing this series, we are delighted to share a tribute to Prof. Shiro Kira, prepared by Prof. Toshihiro Nukiwa.

This series complements our APSR Members' Honour Roll, on which as a member, you are welcome to add your appreciation of your mentor(s) at any time.

Prof. Kira

Prof. Shiro Kira
Recollections of his unique water research surrounding the lung

"Research on water surrounding the lungs" is Prof. Kira's research concept that he often told to his group members. The function of the lung as a respiratory organ is generally gas exchange by air, in and out of the alveoli from the airway. That is, the lungs usually have a persuasive image of air ventilation. However, the lung is also a vascular organ composed of alveolar capillaries whose surface area is to be the entire tennis court. In other words, the lung is a "water" organ as well. The concept of "water surrounding the lungs" includes lung water in health and diseases such as intra-alveolar vessels/extra-alveolar vessels, lung edema, lung injury, pleural effusion, pulmonary hypertension, and even IVC.

Prof. Kira graduated from the University of Tokyo School of Medicine in 1955 and majored in respiratory diseases after residential training. Around 1960s, the progress of cardiac surgery was spectacular and attracted young medical scientists, and it might be partly a reason why Prof. Kira focused on pulmonary circulation. He later noted that it was Prof. Michiyoshi Harasawa's review on pulmonary circulation in Japanese after he returned from US that invited Prof. Kira to pulmonary circulation. Prof Harasawa is of course well known as one of the APSR founders and was Prof. Kira's senior doctor in Tokyo University pulmonary group. The review was so impressive that it described pulmonary circulation such as hypoxic vasoconstriction, cor pulmonale, lung edema and pulmonary thromboembolism.

Prof. Kira studied at the New York State University in Buffalo in 1962 under the recommendation of Prof. Harasawa and studied in the laboratory of Prof. Simon Rodbard. His research there were on the pressure difference in the pulmonary blood in intra-alveolar/extra-alveolar vessels, pulmonary blood vessel capacity, and the relations of the bloodstream (Kira S, Rodbard S, Pulmonary vascular compliances and filtrations. Am Heart J. 1966 ;71(3):371-80., Rodbard S, Kira S, Mechanical forces and pulmonary vascular conductance. Am Heart J. 1966 ;72(4):498-508).

On returning to Japan in 1964, his work on pulmonary circulatory physiology was further developed (Kira S, Hukushima Y, Effect of negative-pressure inflation on pulmonary vascular flow. J Appl Physiol. 1968 ;25(1):42-7), and a new research on impedance plethysmography using pulmonary artery impedance by high-frequency current applied from the chest wall was started (Kira S, et al. Transthoracic electrical impedance variations associated with respiration. J Appl Physiol. 1971 ;30(6):820-6.).

After working as Associate Professor at the Juntendo University in 1972, he was appointed as Professor of Respiratory Medicine at the newly established Jichi Medical University in 1975, where he led both the research and the respiratory clinic. Prof. Kira conducted further clinical application of impedance plethysmography and started the respiratory application of ultrasonic equipment, non-invasive ECHO imaging, which was then introduced into the clinic, and revealed the relationship between central venous pressure (CVP) and collapsibility index through the IVC diameter measurement (Natori H, et al. Ultrasonographic evaluation of ventilatory effect on inferior vena caval configuration. Am Rev Respir Dis. 1979; 120(2):421-7). On the other hand, research on lung injury as non-cardiogenic lung edema due to oleic acid was started with a canine model of unilateral lung injury. Using a unique enzyme activity of angiotensin converting enzyme (ACE) that locates on the alveolar capillary lumen, they reported that injury by oleic acid causes ACE elevation and progress of lung edema (Nukiwa T, et al. Responses of serum and lung angiotensin-converting enzyme activities in the early phase of pulmonary damage induced by oleic acid in dogs. Am Rev Respir Dis. 1982 ;126(6):1080-6.).

Prof. Kira moved to Tokyo as Professor at the Juntendo University in 1985, and further developed a technique for diagnosing respiratory diseases using ultrasound imaging. Using a novel MRI equipment his group showed a correlation between right ventricular hypertrophy index (RVWT/LVPWT) and mean pulmonary artery pressure (Saito H, et al. Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging. Am Rev Respir Dis. 1992 ;146(6): 1576-81.). In addition, as a new research direction that incorporates molecular biology from lung physiology, Prof. Kira launched a new research on pulmonary hypertension using model rats. The project was conducted by doctors back from the Cardiovascular Pulmonary Laboratory, University of Colorado, Denver, USA. Another new direction was based on molecular mutational analysis of α1-antitrypsin deficiency by doctors back from Pulmonary Branch, NHLBI, Bethesda, USA, and they reported a novel deficiency gene, Siiyama, in Japanese population (Seyama K, et al. Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin-deficient variant with mutation on a predicted conserved residue of the serpin backbone. J Biol Chem. 1991 Jul 5;266(19):12627-32.).

At the Juntendo University, Prof. Kira made a major contribution to the spread of home oxygen therapy (HOT) in Japan as Principle Investigator of the Respiratory Failure, a national research project for intractable lung diseases in the Ministry of Health and Welfare. He served as Dean of the Medical Department of the Juntendo University in 1994.

Prof. Kira is very enthusiastic not only in basic respiratory research but also in clinical practice. He attended almost all thoracic surgery cases related to his clinical ward and joined inpatient autopsy examinations. In the clinical data conference for hospitalized cases, the logical step of clinical diagnosis was emphasized, and he always conducted the conference with sharp questions to the presented cases. Through such guidance and education, more than 10 medical professors have been born.

In the Japanese Respiratory Society (JRS), he worked as the director for more than 10 years and served as President of the Annual JRS Meeting in 1994. In APSR, he worked as Secretary General of the first meeting in Tokyo in 1988, the Editor in Chief of "Respirology", an official journal, in 1995, and served APSR President in 2000.

Prof. Nukiwa

Prepared by
Toshihiro Nukiwa, MD, PhD
Professor Emeritus, Tohoku University, Sendai Japan
Chair of the Board Directors, JRS in 2008-2010
President of the Congress of the Asian Pacific Society of Respirology in Yokohama in 2013

August 2019

Dr. Nukiwa first met Prof. Kira while he was at the residential training in 1977. He was impressed by Prof. Kira's comment on the case he presented and joined his group in Jichi Medical University. He was also interested in Prof. Kira's way of thinking as a physician scientist and the way to conceptualize the clinical phenomena. Although Prof. Kira works in physiology and Dr. Nukiwa works in biochemistry and molecular biology, Prof. Nukiwa is proud of being a molecular biologist who can understand VA/Q physiology because he was one of Prof. Kira's mentees.

The August issue (Vol 11.8) features Bronchoscopy:

• How Many Passes Are Needed for Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Sarcoidosis? A Prospective Multicenter Study.
• Endoscopic Ultrasound with Bronchoscope-Guided Fine Needle Aspiration for the Diagnosis of Paraesophageally Located Lung Lesions.
• Impact of Rapid On-Site Cytological Evaluation (ROSE) on the Diagnostic Yield of Transbronchial Needle Aspiration During Mediastinal Lymph Node Sampling: Systematic Review and Meta-Analysis.
• The Evolutional History of Electromagnetic Navigation Bronchoscopy: State of the Art.
• Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases.
• Long-Term Quality-Adjusted Survival following Therapeutic Bronchoscopy for Malignant Central Airway Obstruction.
• Effectiveness of Bronchial Thermoplasty in Patients with Severe Refractory Asthma: Clinical and Histopathologic Correlations.
• A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).
• Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema.
• A Novel Laser Fiberscope for Simultaneous Imaging and Phototherapy of Peripheral Lung Cancer.

Respirology supports World Lung Day on 25 September by making its September edition a Special Issue: Rehabilitation in Chronic Respiratory Diseases

The following cases have been selected for inclusion in the October 2019 Respirology Case Reports, Volume 07 Issue 7

Case Series

Case Reports

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As reported in last month's Bulletin, 1 August was World Lung Cancer Day. Information from FIRS was unavailable when the Bulletin was prepared, but you can read the FIRS press release here.

Don't forget to send photos of your events and activities to the APSR Secretariat APSRinfo@theapsr.org for sharing here in the next Bulletin.

21 August 2019

An article published in the New England Journal of Medicine found associations between short-term exposure to particulate matter (PM10 and PM2.5) and cardiovascular and respiratory mortality risk, from over 600 cities across the globe. [1]

The adverse health effects of short-term exposure to ambient air pollution have been well documented. Particulate matter (PM) raises public health concerns because of its toxicity and the widespread exposure.

This study is an important international effort that evaluates the association of exposure to outdoor fine PM and cardiovascular and respiratory mortality across 652 cities in 24 countries from 6 continents. On average, a 10 mg/m3 increase in two-day moving average of PM10 was associated with increments of 0.44%, 0.36% and 0.47% in total, cardiovascular and respiratory mortality, respectively. The corresponding mortality increments for the same change in PM2.5 were 0.68%, 0.55% and 0.74%.

"This very large data sample allowed researchers to examine the data for obvious confounders while maintaining its statistical power and adjusting for known gaseous pollutants, such as ozone and sulphur dioxide as well as carbon monoxide and nitrogen dioxide." said Clayton T Cowl, MD, MS, President of American College of Chest Physicians and member of the Forum of International Respiratory Societies (FIRS) Environmental Committee. [2]

The most notable finding of the study is related to the exposure-response relationship between PM and mortality. "No threshold level of effect emerges from the data, indicating that at any exposure level a health risk for the exposed population still exists. Moreover, paradoxically, the percentage increase in mortality per 10 mg/m3 increase in PM air concentration is stronger at low exposures than at the highest. This result could be explained by several phenomena ranging from development of a biological 'tolerance' to the adverse health effects of PM in the long-term highly exposed populations to the adaptation of 'avoidance' behaviours (e.g. stay at home on the most polluted days) due to the higher awareness among them of this public health issue," said Sara De Matteis, MD, MPH, PhD, Adjunct Professor at Humanitas University, Honorary Senior Lecturer at Imperial College London, and member of FIRS Environmental Committee. [3]

"Although the study's size gives it strength," warned Teresa To, PhD, Senior Scientist, The Hospital for Sick Children and Professor at the University of Toronto and FIRS Environmental Committee member [4], "the variation across countries may limit its ability to generate a 'general global estimate.' The differences between countries could be from varied exposures of concomitant gaseous pollutants, which add to the toxicity of the PM."

The wide range of the composition of the fine particles (PM2.5) and the different toxins they contain is extremely important and also varies in different regions. Dr Cowl concludes "Studying anything that involves data across the entire planet is difficult and involves attempting to find common denominators for measurements that span geopolitical, programmatic, or individual variation. Despite this, the study shows extremely compelling data that suggest inhalable and fine particulate matter does not just represent a common annoyance but is associated with human mortality most affecting our most vulnerable populations who suffer from underlying cardiac and respiratory illness. It should prompt not only medical providers, but also policymakers to take notice."

Notes

[1] The paper can be viewed at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817364

[2] Dr Clayton Cowl is board certified in Pulmonary, Critical Care, Occupational, and Internal Medicine and is the President of CHEST. He chairs the Division of Preventive, Occupational, and Aerospace Medicine at the Mayo Clinic. He is the Immediate Past-President of the Civil Aviation Medical Association. His research interests are in occupational asthma and toxic inhalations.

[3] Dr Sara De Matteis is Occupational and Environmental Health Physician and epidemiologist whose research centers on the effect of the environment and genetics on health, especially with regard to occupational lung diseases ranging from asthma to lung cancer.

[4] Dr To is a Senior Scientist at The Hospital for Sick Children and a Professor at the Dalla Lana School of Public Health, University of Toronto, whose population-based research focuses on childhood asthma and its environmental influence. She is also at the Institute for Clinical Evaluative Sciences where she works on administrative databases to study healthcare in a variety of medical settings.

Superbugs resistant to emergency antibiotics are spreading in hospitals, a Europe-wide study shows.

Drugs called carbapenems are used when an infection cannot be treated with anything else.

The spread of resistant Klebsiella pneumoniae was "extremely concerning", researchers from the Sanger Institute said. And they warned other bugs could become resistant too, because of the unique way bacteria have sex.

What is Klebsiella pneumoniae?
It can live completely naturally in the intestines without causing problems for healthy people. However, when the body is unwell, it can infect the lungs to cause pneumonia, and the blood, cuts in the skin and the lining of the brain to cause meningitis.

Is it becoming a problem?
Antibiotic resistance has led to a six-fold increase in deaths. Some strains are developing resistance to antibiotics. "The alarming thing is these bacteria are resistant to one of the key last-line antibiotics," Dr Sophia David, from the Sanger Institute, told BBC News. "The infections are associated with a high mortality rate. It's already worrying that we're seeing 2,000 deaths in 2015, but the concern is that if action isn't taken, then this will continue to rise." Deaths from carbapenem-resistant K. pneumoniae have gone up from 341 in Europe in 2007 to 2,094 by 2015. thelancet.com/journals/laninf/article/PIIS1473-3099(18)30605-4/fulltext).

What does the study show?
This is the largest study of carbapenem resistance in K. pneumoniae, with 244 hospitals involved from Ireland to Israel. Researchers analysed the bacterium's DNA - its genetic code - from samples from infected patients. "Our findings imply hospitals are the key facilitator of transmission [and suggest that] the bacteria are spreading from person-to-person primarily within hospitals," said Dr David. "The fact that we see the same high-risk clones in many different hospitals around Europe also shows there's something special about those strains." The results were published in Nature Microbiology. nature.com/articles/s41564-019-0492-8

How big a problem is this?
Drug-resistant K. pneumoniae could continue to spread or pass its resistance on to other species of bacteria. Two bacteria can meet up and have bacterial sex - called conjugation - and a short string of genetic information, called a plasmid, is shared between them. And the study found the instructions that give K. pneumoniae carbapenem resistance written on to plasmids. "These have the ability to spread very rapidly through bacterial populations," said Dr David.

What can be done?
The best way to deal with drug-resistant infections is to avoid getting them in the first place. "We are optimistic that with good hospital hygiene, which includes early identification and isolation of patients carrying these bacteria, we can not only delay the spread of these pathogens, but also successfully control them, said Prof Hajo Grundmann, from the University of Freiburg. "This research emphasises the importance of infection control and ongoing genomic surveillance of antibiotic-resistant bacteria to ensure we detect new resistant strains early and act to combat the spread of antibiotic resistance."

(Extracted from BBC News, 29 July 2019
www.bbc.com/news/health-49132425

In support of Pulmonary Fibrosis Awareness Month, September 2019, Respirology publishes a special collection of PF articles.

The articles will be available from 2 September at: onlinelibrary.wiley.com/page/journal/14401843/pf-awareness-month-2019, and more details can be found at /www.pulmonaryfibrosis.org/get-involved/pf-awareness.

The Centre of Excellence in Severe Asthma has developed a range of freely available resources for severe asthma management.

The Severe Asthma Toolkit is an independent and contemporary online education and training resource that provides multidisciplinary clinicians with the latest information and resources to aid in optimising care for people with severe asthma. The toolkit was developed by a team of multidisciplinary clinicians from Australia, New Zealand and the UK. It was designed to target a broad audience that includes the settings of primary and tertiary care, as well as the many disciplines involved in severe asthma management. It is hoped that the toolkit will allow clinicians in geographically diverse regions to access evidence-based education and training.

The Centre of Excellence has also developed additional practical resources, which are available for download. These include recorded seminars, clinical recommendation documents, assessment checklists and information sheets. Specific recommendation documents have been developed for the use of inflammation biomarkers for assessment and management of severe asthma, monoclonal antibody therapies for severe asthma (omalizumab, mepolizumab and benralizumab) and initiation of monoclonal antibodies in primary care.

Useful links:

• Severe Asthma Toolkit: toolkit.severeasthma.org.au
• About the Toolkit: toolkit.severeasthma.org.au/about
• Educational Seminars: www.severeasthma.org.au/tools-resources/past-webinars
• Clinical Resources: www.severeasthma.org.au/tools-resources/toolkits

Further details: toolkit.severeasthma.org.au/contact

We are honoured to add travel award winner Dr Ho Namkoong to our growing list of travel awardees who will be making significant improvements to respiratory health in the Asia-Pacific region and beyond.

(Keio University School of Medicine, Tokyo, Japan)

APSR Travel Awardee Dr Ho Namkoong joined the ATS International Conference in Dallas, 17–22 May 2019, to present:

Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease (See post-conference report)

A warm welcome to the following members who have recently joined APSR assemblies. They will undoubtedly enjoy working with and networking with their assembly colleagues.

The following members have kindly sent their donation towards the Society's goals, as outlined at apsresp.org/members/donors.php.

• Ahmad Izuanuddin Ismail
• Ashutosh Sachdeva

The APSR is profoundly grateful for their generosity.

Congratulations to Dr Ahmad Izuanuddin Ismail of the Malaysian Thoracic Society, who has recently become an APSR Fellow.

If you have news or announcements that may be of interest to other APSR members, please send details to Bulletin Coordinator Dr Arata Azuma (a-azuma@nms.ac.jp) or APSR Bulletin (bulletin@apsresp.org).