Andrea Trové

The Electronic Nose in Respiratory Medicine

Several volatile organic compounds have been identified in exhaled breath in healthy subjects and patients with respiratory diseases by gas chromatography/mass spectrometry. Identification of selective patterns of volatile organic compounds in exhaled breath could be used as a biomarker of inflammatory lung diseases. An electronic nose (e-nose) is an artificial sensor system that generally consists of an array of chemical sensors for detection of volatile organic compound profiles (breathprints) and an algorithm for pattern recognition. E-noses are handheld, portable devices that provide immediate results. E-noses discriminate between patients with respiratory disease, including asthma, COPD and lung cancer, and healthy control subjects, and also among patients with different respiratory diseases. E-nose breathprints are associated with airway inflammation activity. In combination with other ‘omics’ platforms, e-nose technology might contribute to the identification of new surrogate markers of pulmonary inflammation and subphenotypes of patients with respiratory diseases, provide a molecular basis to a personalized pharmacological treatment, and facilitate the development of new drugs.

Electronic Nose and Exhaled Breath NMR-based Metabolomics Applications in Airways Disease

Breathomics, the multidimensional molecular analysis of exhaled breath, includes analysis of exhaled breath with gas-chromatography/mass spectrometry (GC/MS) and electronic noses (e-noses), and metabolomics of exhaled breath condensate (EBC), a non-invasive technique which provides information on the composition of airway lining fluid, generally by high-resolution nuclear magnetic resonance (NMR) spectroscopy or MS methods. Metabolomics is the identification and quantification of small molecular weight metabolites in a biofluid. Specific profiles of volatile compounds in exhaled breath and metabolites in EBC (breathprints) are potentially useful surrogate markers of inflammatory respiratory diseases. Electronic noses (e-noses) are artificial sensor systems, usually consisting of chemical cross-reactive sensor arrays for characterization of patterns of breath volatile compounds, and algorithms for breathprints classification. E-noses are handheld, portable, and provide real-time data. E-nose breathprints can reflect respiratory inflammation. E-noses and NMR-based metabolomics of EBC can distinguish patients with respiratory diseases such as asthma, COPD, and lung cancer, or diseases with a clinically relevant respiratory component including cystic fibrosis and primary ciliary dyskinesia, and healthy individuals. Breathomics has also been reported to identify patients affected by different types of respiratory diseases. Patterns of breath volatile compounds detected by e-nose and EBC metabolic profiles have been associated with asthma phenotypes. In combination with other -omics platforms, breathomics might provide a molecular approach to respiratory disease phenotyping and a molecular basis to tailored pharmacotherapeutic strategies. Breathomics might also contribute to identify new surrogate markers of respiratory inflammation, thus, facilitating drug discovery. Validation in newly recruited, prospective independent cohorts is essential for development of e-nose and EBC NMRbased metabolomics techniques.

Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P  <  0.02; healthy subjects: P  <  0.03), whereas EBC PGE2 was elevated in current (P  =  0.0065) and ex-smokers with COPD (P  =  0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P  <  0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P  <  0.01; healthy subjects: P  <  0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P  =  0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study

Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5‐year follow‐up.

Polymorphism of Beta2-Adrenoceptor and Regular Use of Formoterol in Asthma: Preliminary Results

Polymorphism at codon 16 of the beta2-adrenoceptor (beta2-AR) affects the responsiveness to salmeterol in asthmatics. Data concerning formoterol are more controversial in the literature. The aim of this study was to verify whether homozygous for arginine-16 (ArgArg16) and homozygous for glycine-16 (GlyGly16) genotypes differently influence the long-term responsiveness to formoterol. Twenty-nine patients with mild-to-moderate asthma, in stable clinical conditions, underwent genotyping at codon 16 of the beta2-AR by RFLP-PCR assay. The effects of a 4-week monotherapy with formoterol (12 μg BID) were tested on the peak expiratory flow (PEF) variability and the forced expiratory volume in 1 sec (FEV1) slope of the dose-response curve to salbutamol. Variability in PEF significantly increased during the 4-week treatment period in 14 patients with GlyGly16, but not in 15 patients with ArgArg16 and ArgGly16 . The FEV1 slope of the dose-response curve to salbutamol decreased after the 4-week treatment period in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients. This study provides preliminary evidence that tolerance to formoterol develops more frequently in asthmatics with GlyGly16 genotype. If confirmed in a larger population, this finding might be useful in choosing the bronchodilator therapy on the basis of genetic polymorphism of the beta2-AR.

Chris T. Bolliger: An Obituary

bronchoscopy and thoracoscopy, both diagnostic and therapeutic. Other interests of his were cardiopulmonary exercise testing and tobacco control with emphasis on smoking cessation. Over time, he published more than 250 articles, 14 books, and various book chapters. One of his initial publications [1] remains the basis of our daily treatment decisions in lung cancer patients. In addition to all of his clinical and research work, in 1998 he took over the position of editor-in-chief of Respiration. In the following years, he developed the journal After an acute illness Chris T. Bolliger, Director and Head of the Respiratory Research Unit and Cohead of the Division of Pulmonology of the Department of Medicine of the University of Stellenbosch, Capetown, South Africa, died on November 2, 2012, at the age of 62. With him, we have lost an experienced medical doctor as well as a friend. His great expertise and humanity towards his patients and colleagues will be sorely missed. Chris T. Bolliger was born in Switzerland. He went to medical school in Basel and Lausanne and graduated in 1976. Subsequently he finished his residency and fellowship in internal medicine with a subspecialty in pulmonology. He moved to South Africa in the early 1980s and earned a Baccalaureus with Honors (Hon. BsC) in epidemiology at the University of Stellenbosch in 1989. He then went back to Switzerland in the same year and became a consultant in the Division of Pulmonology of the University Hospital of Basel. During that time, he finished his PhD and obtained his associate professorship. In 1999, he moved back to the Faculty of Health Sciences of the University of Stellenbosch, where he was appointed cochairman of the Pulmonology Division and director of the Respiratory Research Unit. In both his research and his clinical work, he set very high standards for himself and those working with him. Most recently, he was the director and head of the Respiratory Research Unit of the Department and cohead of the Division of Pulmonology of the Department of Medicine of the University of Stellenbosch. From the beginning he developed an ongoing interest in clinical and basic research. Initially he focused on thoracic oncology with special emphasis on interventional Published online: December 13, 2012

In Memoriam Christoph T. Bolliger

board members and friends of the journal informed of the latest developments and changes to the journal. He also successfully edited the book series Progress in Respiratory Research where he initiated many outstanding and award-winning volumes of which some have become true classics in the field such as Interventional Bronchoscopy and Clinical Chest Ultrasound . Over the years, a very close and pleasant collaboration developed with the publishing house and he became a valued advisor in publishing matters. We appreciated his friendly way to motivate people, his humour, his inspiration, his deep insight and clear vision for the journal and the book series. Chris Bolliger’s sudden and untimely passing on November 2 shocked the entire editorial team of Respiration . We have lost a true leader and an extremely successful Editor, a very warm-hearted person so full of life and energy. A part of Professor Christoph Bolliger remains in all of us who had the privilege to work with him. As one of the Associate Editors of the journal so correctly wrote: ‘You can replace the Editor-in-Chief, but you cannot replace this wonderful man’. He will be sorely missed by all of us and we will do everything to secure the journal’s future and foster its reputation as one of the leading journals in the field. Thomas Nold, Thomas Karger and Gabriella Karger and the Respiration team The publisher and the editorial staff of Respiration would like to express their sadness at the sudden passing of Professor Christoph T. Bolliger. We were first introduced to Chris Bolliger by Professor Heinrich Herzog, who invited him to join the Editorial Board of the journal Respiration back in 1995. In January 1998, Professor Bolliger officially became the new Editorin-Chief of Respiration . Full of enthusiasm about his new role, he announced his visions for the future of the journal in the first of his many editorials which was entitled ‘A Wind of Change’. Chris Bolliger was not just an excellent clinician and scientist, but also a passionate editor, who had many excellent ideas for the journal and the commitment and perseverance to realise his aims to the full. Thanks to his international network he was able to provide feedback on the latest trends in medical publishing and he was continuously striving to improve the quality of the journal. During the 15 years of his editorship, the number of submissions increased by almost 300%, the impact factor climbed up to 2.5 and the rejection rate increased from 43 to 76%. We saw the introduction of many new sections to the journal, e.g. Thematic Review Series, The Eye Catcher, and Interventional Pulmonology. He ensured the journal had a truly diverse group of dedicated Associate Editors covering all fields of respiratory medicine, supported by an international Editorial Board. Dr. Bolliger’s very popular newsletter ‘News in a Nutshell’ was put out twice a year to keep authors, reviewers, editorial Published online: December 13, 2012

The European Association for Bronchology and Interventional Pulmonology Is in Mourning

His untimely death did not befit his young mind and soul with endless energy and enthusiasm. We are deeply sad and in shock and will miss him so much ... But we will never forget him and his achievements by carrying them to a higher level that he would love to see. We send our cordial condolences, concerns and sympathies to his family and wish them much strength, endurance and a lot of support for the upcoming time.

Prof. Dr. med. Chris T. Bolliger

From 1999, he was associate professor and since 2002 full professor at the University of Stellenbosch in South Africa. Chris Bolliger was very active in the scientific world and published over 200 works including original papers, review articles and many articles in book series. He was active in the scientific organization of the European Respiratory Society for over 12 years and held various high positions until he reached Head of Clinical Assembly. As Editor-in-Chief of the journal Respiration , he put all his strength and effort into the furthering of the journal, and the good position the journal has achieved in the scientific world is largely due to his contributions over the years. Within his specialty field, he engaged himself significantly with interventional pulmonology and recently helped his colleagues in the organization of the first European congress on the topic. Professor Chris Bolliger has left a big hole in the clinical and scientific world both as a friend and as a colleague and we will miss him very much. He leaves behind a wife and three children and we would like to offer his family our heartfelt condolences.