Should lung biopsies be performed in patients with severe asthma?

Abstract

Asthma, and severe asthma, in particular, is increasingly recognised as a heterogeneous disease. Identifying these different phenotypes of asthma and assigning patients to phenotype-specific treatments is one of the current conundrums in respiratory medicine. Any diagnostic procedure in severe asthma (or any disease) should have two aims: 1) better understanding or identifying the diagnosis, and 2) providing information on the heterogeneity of asthma phenotypes to guide therapy with the objective of improving outcomes. Lung biopsies can target the large and small airways as well as the lung parenchyma. All compartments are affected in severe asthma; however, knowledge on the distal lung is limited. At this point, it remains uncertain whether lung specimens routinely add diagnostic information that is unable to be obtained otherwise. Indeed, whether a lung biopsy is indicated in the workup of a patient with severe asthma remains an individual decision. It is hoped this review will support rational decision-making and provide a detailed synopsis of the varied histopathological features seen in biopsies of patients with a diagnosis of severe asthma. Due to limited data on this topic this review is primarily based on opinion with recommendations arising primarily from the personal experience of the authors.

FIGURE 1.

Examples of “classical” small airway disease in severe asthma from video-assisted thoracoscopic surgery procured tissue showing small airways with epithelial hyperplasia and mucous plugs (black squares), prominent smooth muscle hyperplasia/hypertrophy (asterisks), thickened basement membrane (arrowheads) and adventitial eosinophilic/lymphocytic inflammation extending into areas of alveolar attachments (arrows). a) 100× magnification, b) 400× magnification.

FIGURE 2.

Outline of the distal lung regions in haematoxylin and eosin-stained lung tissue [115, 116] showing the inner airway wall (green arrowheads), smooth muscle (SM), outer airway wall (blue arrows) and alveolar attachment (black arrows).

FIGURE 3.

Examples of distal lung disease in “atypical” severe asthma and differential diagnoses from video-assisted thoracoscopic surgery procured tissue. a) Small airway with massive lymphocytic bronchiolitis (arrowheads) often found in severe asthma with an autoimmune background (100× magnification). b) Small interstitial poorly defined granulomas (arrows) with epitheloid histiocytes/giant cells (arrowheads) in asthmatic granulomatosis, note the absence of vasculitis (100× magnification). c) Granulomatous inflammation in eosinophilic granulomatosis with polyangiitis, note the presence of prominent tissue eosinophilia, vasculitis (arrow) and necrotising granulomatous inflammation (arrowheads) (200× magnification). d) Aspiration granuloma, note a well-formed, non-necrotising granuloma entirely replaces an airway lumen (arrow), with foreign-body giant cell reaction to vegetable material (arrowhead) (100× magnification).