Diffuse parenchymal lung disease (DPLD), also known as interstitial lung disease, encompasses a broad heterogeneous group of nonneoplastic disorders that affect the lung parenchyma, predominantly the interstitium but also to some extent the airspaces, peripheral airways, and vessels. This includes not only diseases with known etiologies and/or well-defined clinical pathologic features such as pneumoconiosis, sarcoidosis, pulmonary Langerhans cell histiocytosis (PLCH), or lymphangioleiomyomatosis (LAM) (Table 16.1) but also a group of diseases referred to as “idiopathic interstitial pneumonia” (IIP).^1,2

IIP is used for a subset of DPLD of unknown cause (Table 16.2).³ Historically, the concept of IIP began with the description of rapidly progressive, idiopathic interstitial fibrosis with mononuclear inflammation (“Hamman-Rich syndrome”).^4,5 The recognition that the alveolar spaces were affected in organization of interstitial lung disease led to the term “diffuse fibrosing alveolitis,”⁶ which was categorized as secondary to inhalational agents or drugs and idiopathic.⁷ Subsequently, the term “cryptogenic fibrosing alveolitis” was used by clinicians usually for chronic interstitial pneumonias, but they occasionally included more acute processes. Idiopathic pulmonary fibrosis (IPF) was introduced as a synonym for cryptogenic fibrosing alveolitis, and soon both terms came to encompass several pathologic entities including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD), and organizing pneumonia (OP), leading to much confusion in the classification of IIP. In 2002, IPF was officially restricted to cases of UIP. In the United States, cryptogenic fibrosing alveolitis is not used, leaving IPF as the sole clinical term for patients with a histologic diagnosis of UIP.

The other major contributing factor to the confusion of the IIP classification has been the use of different terms by clinicians and pathologists. The 2002 ATS/ERS multidisciplinary consensus classification established a new classification that correlates both the clinical and pathologic diagnoses.¹ This classification was recently updated (Table 16.2).⁸

The consensus classification provides the basis for a multidisciplinary clinical-radiologic-pathologic diagnosis with the purpose of improving the accuracy of the diagnosis. Indeed, there is not a high level of reproducibility among pathologists in assessing interstitial lung disease.^9,10 The increased interactions between pathologists, radiologists, and clinicians have shown to improve the overall diagnosis compared to each group individually.¹¹ Nevertheless, there remains a subset of unclassifiable IIP, for various reasons such as inadequate pathology; major discordance between the pathologic, radiologic, or clinical findings; or prior treatment effect.

The prevalence of all DPLD is ˜81 per 100,000 people.¹² The most common diagnosis is pulmonary fibrosis (not otherwise specified), with a prevalence of 30 per 100,000, without sex predilection. Occupational lung disease is by far more common in men than women, with a prevalence of 21 per 100,000 in men. DPLD associated with connective tissue disease is seen at a prevalence of ˜10 per 100,000 and is somewhat higher in women. Pulmonary sarcoidosis’ prevalence is 9 per 100,000 without gender predilection.¹²

Typically, DPLD results in restrictive lung defects, which are manifested by decreased forced vital capacity (FVC) and impaired gas change. In contrast to obstructive lung disease, the ratio of the FEV1 (forced expiratory
volume in 1 second) to the FVC is relatively spared, as there is a concomitant decrease in FVC. The mechanism of decreased FVC, total lung volume, and FEV1 is directly related to the mechanical effects of scarring of the lung parenchyma. There are several types of DPLD with an obstructive component, characterized by decreases in FEV, especially at one second or in midexhalation, as a fraction of FVC, and bronchiolar hyperreactivity. These include sarcoidosis, hypersensitivity pneumonia, PLCH, and LAM.