Are Bronchioles Fueling Burning Alveoli in Lung Fibrosis?

Abstract

Although narrowing and stenosis of the small airways were noted in the original description of IPF by Hamman and Rich [5] , subsequent morphologic studies have largely concentrated on the alveoli and alveolar interstitium, perhaps because the significance of small airway abnormalities in the pathophysiology of chronic fibrotic pulmonary disorders was hardly recognized. In a seminal work comparing physiologic and morphologic observations in 18 patients with what was called IPF at that time, Fulmer et al. [6] clearly demonstrated morphologic and physiologic changes in the small airways of patients with mid-course fibrotic lung disease – in both smokers and non-smokers. Morphologically, they described a pattern of peribronchiolar fibrosis and inflammation without significant bronchiolitis, leading to their conclusion that fibrosis of the small airways is secondary to the interstitial process. Physiologically, commonly employed methods for assessing small airway disease, e.g. the single breath nitrogen test and closing volume determination, proved not useful in patients with fibrotic disease probably because of the increase in the elastic recoil associated with the disease. By contrast, abnormalities in dynamic lung compliance and alterations in maximal expiratory flow volume curves were strongly associated with airway narrowing in those patients. Interestingly, the overall estimate of airway narrowing neither correlated with total lung capacity nor with vital capacity, functional residual capacity or carbon monoxide transfer. Altogether, these Sometimes humans refuse to look at the world as it is and prefer to see the world as it should be, but hopefully, sometimes someone turns up and leads us back to the right path. I suspect that it is exactly the role of George Castro Figueira de Mello and his colleagues in this issue of Respiration , taking us by the hand to bring us back to basics [1] . What they remind us of is obvious: alveoli are linked to bronchioles. This is so evident that most of us just forgot it when thinking of lung fibrosis. In the most popular dogma, lung fibrosis is regarded as impaired communication between alveolar epithelial cells and fibroblasts [2] . Although this pathophysiological model renewed our thinking about the disease, it did not consider several important components of the respiratory system such as blood vessels, the pleura and, indeed, the bronchial tree. Fortunately, this is a time for rediscovery. Alterations in the pulmonary circulation in lung fibrosis are being illuminated and this may translate into therapeutic advances for patients [3] . At the same time, pleural mesothelial cells were ascribed a role in the pathophysiology of pulmonary fibrosis, particularly via mesothelial-mesenchymal transition [4] . This is particularly important for idiopathic pulmonary fibrosis (IPF), a disease that begins and predominates in the subpleural regions of the lung. In their study, our Brazilian colleagues remind us that lobules encompass bronchioles, and that small airways are involved in the fibrotic disease. Published online: December 17, 2009