Fig. 30.7  Lung parenchyma showing an interstitial and alveolar infltrate rich in eosinophils (H&E, mid-power)

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Clinical Vignette

A previously healthy 67-year-old male former smoker of 25 pack-years reports worsening exertional dyspnea and an occasionally productive cough. An initial evaluation for potential cardiac etiologies does not reveal any obvious cause and the patient subsequently undergoes a pulmonary function test (PFT) and chest computed tomography (CT). The PFT reveals slightly reduced ow rates and lung volumes in a restricted pattern, with a diffusion capacity of the lung for carbon monoxide of 62% predicted. The CT shows peripheral and lower lung predominant reticulation and traction bronchiectasis without honeycombing, nodularity, ground glass, or mosaicism. The community radiologist reports this as a possible usual interstitial pneumonia pattern based on previous clinical practice guidelines, and the patient is considered to have unclassifable ILD by his initial respirologist given the absence of a clear cause and an inconclusive imaging pattern.

The patient is referred to an ILD center and has an extensive assessment that more confdently excludes the possibilities of fbrotic hypersensitivity pneumonitis, connective tissue disease-associated interstitial lung disease (ILD), or drug-induced ILD. A multidisciplinary discussion is performed in collaboration with an experienced chest radiologist who concludes that the CT pattern is that of probable UIP using the updated contemporary clinical practice guidelines. On that basis, the patient is provided a working diagnosis of

C. J. Ryerson (*)

Department of Medicine, University of British Columbia, Vancouver, BC, Canada

Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC, Canada

e-mail: chris.ryerson@hli.ubc.ca

idiopathic pulmonary fbrosis (IPF) and a surgical lung biopsy is felt to be unwarranted in that context. The patient is offered and agrees to start taking an antifbrotic medication.

Introduction

Interstitial lung disease (ILD) is a collection of approximately 200 diverse conditions that result in in ammation and/or fbrosis of the lung parenchyma. Common fbrotic ILD subtypes include idiopathic pulmonary fbrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and fbrotic hypersensitivity pneumonitis (HP), with a substantial percentage, also considered to have an unclassifable ILD. Fibrotic ILDs are chronic and progressive diseases that are frequently characterized by disabling dyspnea and cough, reduced quality of life, and early mortality. The prognosis of IPF, which is the most common idiopathic interstitial pneumonia (IIP), appears to be improving with slightly longer median survival in recent cohorts (3–5 years from the time of diagnosis) compared to the historical median survival of 2–3 years [1]. The incidence and prevalence of common fbrotic ILDs are also increasing [2], although it is not clear whether this reported increase is simply a consequence of greater recognition.

Distinguishing ILD subtypes is challenging, often requiring a multidisciplinary effort by an experienced team of ILD clinicians, chest radiologists, and lung pathologists [3, 4]. This multidisciplinary discussion (MDD) of relevant clinical, radiological, laboratory and histopathological features is best accomplished with a face-to-face dynamic interaction of these subspecialists. Previous studies have suggested higher diagnostic accuracy, represented by greater diagnostic agreement, in academic centers compared to healthcare providers working in community settings [5]. Diagnoses assigned by experienced physicians working in academic centers similarly carry greater prognostic signifcance compared to diag-

noses by less experienced clinicians, also suggesting higher diagnostic accuracy among experts [6]. The clinical impact of the MDD approach is illustrated by the change in diagnosis and change in treatment for approximately 50% of patients subjected to this process [7, 8].

In this chapter, key components of the clinical, radiological, laboratory, and bronchoscopic and histopathological assessment are discussed, followed by a review of the typical approach to the integration of these features. This chapter focuses on fbrotic ILD subtypes given the more frequent diagnostic challenges that are encountered with these diseases. The specifc features of each major ILD subtype are provided in the chapters that address each of these diagnoses.

Overview of ILD Diagnosis

Patients with fbrotic ILD typically present with chronic onset of dyspnea that becomes noticeable over several months or even years. Unless ILD is detected incidentally, dyspnea is almost universally present at the time of diagnosis. Approximately 85% of patients also report chronic cough at the time of diagnosis, which can be even more disabling than dyspnea in some patients [9]. These symptoms and associated functional limitations are nonspecifc, with more frequent etiologies such as chronic obstructive pulmonary disease (COPD) and heart disease typically being considered by general practitioners prior to identifcation of ILD on chest imaging. As a consequence, patients with ILD are frequently provided one of these incorrect diagnoses based on an incomplete evaluation, and frequently spend months and sometimes years being ineffectively treated for these conditions before the correct diagnosis is made. Aside from the emotional toll that accompanies a missed diagnosis [10], these delays can have a signifcant prognostic impact with worse survival in patients who have a delayed referral to an experienced ILD center [11]. It is therefore important that general practitioners consider ILD in their differential diagnosis of new unexplained dyspnea, cough, or functional limitation, potentially using some of the clinical features described below to help identify these patients at an earlier stage of their disease.

Once ILD is considered, patients will typically undergo a pulmonary function test and chest imaging. Based on their relative availability and lack of radiation exposure, pulmonary function tests are often used as a screening tool for patients at risk for ILD or as the frst test in patients with a new suspected ILD; however, many patients with early ILD

have normal pulmonary function tests or only a mild isolated reduction in gas transfer (i.e., a reduced diffusion capacity of the lung for carbon monoxide [DLCO]). Pulmonary function tests are therefore not sensitive nor specifc enough to rule in or rule out ILD in many of the more common clinical scenarios.

The defnitive tool used to identify the presence of an ILD is computed tomography (CT), with most conventional CT scanners now providing the appropriate high-resolution images that are needed to adequately characterize ILD morphology. ILD can be subclassifed radiologically into fbrotic and non-fbrotic forms, with non-fbrotic subtypes of ILD including a variety of in ammatory, cystic, and nodular processes. Within each of these main ILD patterns, there are additional sub-patterns that further narrow the differential diagnosis, with many of these sub-patterns being diagnostic when considered in the corresponding clinical context. For example, patients with usual interstitial pneumonia (UIP) pattern without an underlying identifed etiology after a thorough clinical and laboratory evaluation can be provided a confdent diagnosis of IPF without the need for tissue confrmation [12].

The specifc diagnostic criteria for each ILD subtype are provided in the corresponding chapters, with the remainder of this chapter focusing on the general approach that applies across the full spectrum of clinical settings and how various features should be integrated in order to arrive at a fnal diagnosis.

Clinical Assessment

There are no clinical features that are pathognomonic for ILD. Dyspnea, cough, and functional limitation are frequent manifestations of ILD, but are also observed in other more common diseases such as COPD and heart disease. The presence of a family history of ILD, hypoxemia, auscultatory crackles, or clubbing are nonspecifc features, but should prompt consideration of fbrotic ILD in patients with chronic dyspnea, cough, or functional limitation. Importantly, auscultatory crackles are not typical fndings of asthma, COPD, or CHF other than during acute exacerbations or episodes of volume overload. Hypoxemia and clubbing are not common fndings in these conditions and also indicate the need to consider alternative or additional diagnoses. The initial evaluation in patients with any of these high-risk features should typically include complete pulmonary function tests (preand post-bronchodilator spirometry, lung volumes, and DLCO) and CT imaging of the chest. Patients with features suggesting a predisposing condition (e.g., connective tissue