Vincent Cottin ·

Luca Richeldi · Kevin Brown ·

Francis X. McCormack Editors

Orphan Lung

Diseases

A Clinical Guide to Rare Lung Disease

Second Edition

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Preface to the First Edition

So-called orphan diseases are those conditions that attract little interest by physicians and scientists, which are not widely researched, and where specifc treatments are lacking. Orphan diseases are nevertheless characterized by particularly high needs and expectations from patients, who feel abandoned in the world of health care and expect their treating physician to make every possible effort to help them by managing at best their disease. However, as one cannot expect physicians to be knowledgeable with each of the 6000–8000 orphan diseases, they generally lack experience of most orphan diseases and are left with insuffcient knowledge to manage these patients. Indeed, most orphan diseases are rare, at least in Europe and North America. Not all orphan diseases are rare, however, and especially neglected tropical infectious diseases are endemic in Africa, Asia, and the Americas, affecting one billion people worldwide and causing tremendous morbidity and mortality.

Rare diseases are defned numerically. In Europe, a disease is rare if it affects fewer than 1 person in 2000. In the USA, a rare disease is a disease that affects fewer than 200,000 people or that affects more than 200,000 but for which there is no reasonable expectation to be economically proftable, with the cost of drug development and availability for such a disease to be recovered from sales. Overall, given the plethora of different conditions, rare diseases are a major health-care burden worldwide. Regarding lung medicine alone, it is estimated that 1.5–3 million Europeans and 1.2–2.5 million Americans are affected by a rare lung disease.

Despite the many diffculties and obstacles, the new millennium witnessed an astonishing gain in the momentum to improve our understanding and the management of many rare diseases, some of which are, therefore, no longer orphan. Interest in rare diseases has increased greatly worldwide. Patients with orphan diseases have joined associations providing them with a previously unknown sense of community, unprecedented awareness, and strong advocacy for more research and better treatments. A steadily increasing number of international organizations and websites contribute to education, support, and research. Governments and agencies have introduced incentives to encourage the pharmaceutical industry to invest in research despite the small target populations. Specialized centers and clinical networks are now developing and have been identifed in many countries: This crucial step provides up-to-date management to patients, allows basic and clinical research, establishes registries, interacts with regulatory agencies, and supports patient associations. Novel conditions and syndromes are discovered. The genetic determinants of many diseases and their underlying pathophysiology are progressively better understood. An increasing number of drug candidates are identifed and may be granted an orphan drug designation with more clinical trials completed, thereby leading to the approval and licensing of drugs in diseases heretofore considered not treatable. Diseases such as pulmonary arterial hypertension and idiopathic pulmonary fbrosis, formerly devoid of any treatment, are now treatable although they are still deadly severe and not curable.

In this context, diagnosing and managing patients with orphan pulmonary diseases is an increasing challenge to pulmonologists and internal medicine specialists as it is increasingly diffcult to keep up to the current pace of growth of knowledge, especially in basic science. To witness the evolution of this feld is tremendously stimulating since progress made in pathophysiology, organization of care, and management rapidly translates into clinical practice for

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Preface to the Second Edition

The frst edition of Orphan Lung Diseases: A Clinical Guide to Rare Lung Disease was published in 2015. The book was very well received, as rare lung diseases are increasingly attracting attention, especially in the context of very active research on new treatments, with the milestone represented by the approval in 2014 of antifbrotic drugs to treat idiopathic pulmonary fbrosis. The book covers the feld of rare pulmonary diseases as a whole, and not just interstitial lung diseases, which of course represent the largest share. Due to the progress in the feld, the variably limited number of patients with each condition, and the number of conditions involved, it is very diffcult for clinicians to remain current in this feld. However, patients with rare pulmonary diseases collectively represent a signifcant fraction of the patients followed by practicing pulmonologists, as well as rheumatologists, internists, and other specialists. With the possible exception of idiopathic pulmonary fbrosis and progressive pulmonary fbrosis, rare pulmonary diseases typically receive less attention by clinicians, researchers, and industry than those more frequently seen in daily clinics. This textbook is oriented toward clinical practice and is accessible online, to provide busy practitioners with ready access to information needed in a timely manner.

The main change for the second edition is that the number of chapters has been increased from 36 in the previous edition to the current 43, now divided into seven parts. This enabled us to create new chapters on topics that have become increasingly relevant, such as pleuropulmonary fbroelastosis, unclassifable interstitial lung disease, complex thoracic lymphatic disorders of adults, and interstitial pneumonia with autoimmune features and overlap interstitial pneumonia. The parts on interstitial lung diseases and on systemic disorders with lung involvement have been expanded to better cover these important felds, and new chapters were created on diagnostic modalities, including separate chapters on imaging, bronchoscopic and integrated diagnostic approaches to interstitial lung diseases. A new part on rare lung diseases of genetic origin has been included: genetic and familial pulmonary fbrosis related to monogenic diseases, diffuse bronchiectasis of genetic or idiopathic origin, pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia, pulmonary alveolar microlithiasis, and rare diffuse lung diseases of genetic origin. Although no book could hope to cover the immense and ever-growing area of rare pulmonary diseases, we welcome suggestions for the next edition.

The editorial board was joined by two new editors, Dr Kevin K. Brown and Dr Francis McCormack, who brought new ideas and expertise. As Prof. J.F. Cordier has now retired, this new edition was supervised by four editors. We also welcome new authors coming from a variety of countries and regions. As in the previous edition, our goal in this book was to synthesize and organize emerging clinical and research advances in an easily accessible format that is oriented toward the practicing clinician. We thank all authors who have dedicated time to this textbook, and have provided clinically oriented manuscripts, comprising numerous illustrations, representative case examples, and guidance for both the diagnostic process and the practical management, often without the luxury of offcial diagnostic criteria or guidelines.

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