Contents

Defnitions

The term “orphan” has been coined to describe rare diseases because of the affected sense by patients that many physicians are uncomfortable with the management of their disease, and, as such, hope for the future is dim because so little research has been devoted to understanding such rare disorders in patients and improving their quality of life [1]. Their feeling of abandonment is intensi ed by comparisons with patients who suffer from common diseases and who bene t from extensive research and continuous drug development. The struggle for equal access to care and research by patients and the organizations that represent them is common to all orphan lung diseases. The associated ethical and social issues are complex and drive many of the particularities of how the care for these conditions is organized. In fact, in some countries, patients have a legal right to equal access to health care, regardless of the epidemiology of their condition [2].

The de nition of a rare disease in Europe is a condition with a prevalence of less than 1 in 2000 people (equivalent to a prevalence of less than 50 in 100,000 people) and affecting fewer than 200,000 people in the USA (which equates to about 1 in 1700 people). Although arbitrary, these de nitions are not trivial, as they have practical implications for all stakeholders including patients, regulatory bodies, drug developers, and payers (Fig. 1.1). In contrast, currently, there is no established de nition for the so-called “ultra-rare” diseases, which affect even smaller populations, with a prevalence as low as 1 in 2,000,000 or even less [1]. The distinction

between “somewhat rare” and “ultra-rare” lung diseases is useful to consider. Somewhat rare diseases include conditions that may or may not t the de nition of a rare disease, depending on the epidemiological method used or geographic or ethnic disparities (e.g., sarcoidosis) [3, 4]. This category of ultra-rare lung diseases was introduced by the National Institute for Health and Care Excellence for drugs with indications for diseases that have a prevalence of <1 per 50,000 persons [2]. Studies in ultra-rare lung diseases must be conducted at a national or regional level to assemble even a handful of patients, which poses major challenges to conducting clinical trials of robust methodology [5, 6]. Examples of rare lung diseases in this category would include pulmonary alveolar microlithiasis [7], pulmonary alveolar proteinosis of genetic origin [8], light chain deposition disease [9], ataxia telangiectasia [10], Birt–Hogg–Dubé syndrome [11], and others.

It is worthwhile mentioning that not all orphan diseases are rare. Some conditions may be common but neglected because they affect people in poor countries (e.g., chronic infectious tropical diseases) [12]. Conversely, not all rare diseases are orphan, as progress in organization of care and research can eventually lead to progress in the management of rare diseases, sometimes with highly active research in networks of specialized centers and ef cient drug development. Examples of rare lung diseases, which to some may not be considered orphan anymore, include idiopathic pulmonary brosis, pulmonary arterial hypertension, and lymphangioleiomyomatosis (LAM).

Fig. 1.1  The main stakeholders in the care of patients with orphan lung diseases

Diagnosis

Management

Monitoring

Medical education

Patients’

support,

education, and advocacy

Research

•Accurate and timely diagnosis

•Multidisciplinary discussion

•Access to specialty resources

•Pharmacologic and nonpharmacologic management

•Treatment decisions based on guidelines and expert opinion

•Multidisciplinary discussion of management

•Infrastructure to provide comprehensive care

•Longitudinal monitoring to inform management decisions

•“Shared-care” model of care between local pulmonologists and expert centres to facilitate timely access to care, minimise patient travel, and “off-load” specialty clinics

•Medical education for clinicians and trainees

•Research on knowledge gaps and effective education strategies

•Patient education, support, and advocacy as a key component of specialized centers.

•Facilitate direct patient interaction and community engagement.

•Access to clinical trials

•Infrastructure, momentum, and commitment to research

The Wide Spectrum of Rare Pulmonary

Diseases

The number of “all” rare diseases and syndromes has not been hitherto established, although rough estimates range

between 6000 and 8000, with a large proportion being of genetic origin. Despite being rare, “collectively” rare diseases may affect up to 5% of the population, translating into ~30 million in Europe and the USA [1]. Although most rare “lung” diseases are idiopathic and chronic rather than of