Idiopathic Pulmonary Fibrosis: Time to Get Personal?

Abstract

in the CF piglet. Because the timing of fetal CFTR expression in the mammalian lung is synchronous with the branch development of the large airways, the authors submit that the findings observed in the CF piglet are a direct correlate of CFTR dysfunction and not reduced fetal lung liquid or impaired chloride secretion. They also suggest that absent CFTR function affects a host of cells, including chondrocytes, smooth muscle, and neural cells.The findings of Adams and colleagues (10), if they indeed occur in young children with CF, support a growing concept that ventilation heterogeneity per se is fundamental to the pathobiology of lung disease. In study participants with asthma, the magnitude of ventilation heterogeneity measured by lung clearance highly informs the degree of bronchial hyperresponsiveness, better than biomarkers of inflammation, and predicts asthma control after up-and down-titration of inhaled corticosteroid treatment (13,14). Repeated exposure of individuals with stable asthma to methacholine-induced bronchospasm induced early structural changes of airway wall thickening (15). The results of this study suggest that the compressive mechanical forces attendant to bronchospasm support regional airway remodeling independent of inflammation. These provocative findings highlight the fact that the relationship between regional lung inflammation and lung function is not well understood. The mandate is clear for innovative studies examining such relationships (16). Exciting new imaging methods, including positron emission tomography, hyperpolarized noble gas MRI, and single-photon emission computed tomography, coupled to image-guided bronchoalveolar lavage and biopsy, will foster new understanding of the pathobiology of lung disease. The result will be a paradigm shift away from the conception of diseases like CF and asthma as involving the entire lung to an informed understanding of regional pathology linked to significant ventilation heterogeneity.

Bacterial and viral coinfection in idiopathic pulmonary fibrosis patients: the prevalence and possible role in disease progression

“…It has previously been shown to bind dsRNA from viruses, bacteria and helminths, respectively, in addition to mRNA released from necrotic cells [29][30][31][32]. Recently, our laboratory demonstrated that the TLR3 SNP, Leu412Phe (TLR3 L412F, rs3775291), which results in defective TLR3 function, is associated with a significantly greater risk of mortality and an accelerated rate of decline in FVC of lung function in IPF patients [26,33]. Our recent data demonstrates that 412F-heterozygous IPF patients have reduced responses to viral dsRNA and a number of bacterial agonists [26].…”

Pathogenesis of idiopathic pulmonary fibrosis: review of recent findings

“…Furthermore, the variant was associated with disease progression or early mortality (or both) in two separate IPF cohorts, with an additive effect for each allele [76]. This study is another example of a genetic variant linked to outcome in IPF and highlights the possibility of differences in response to treatments in different subsets, as suggested by the editorial accompanying the article [77]. The activation of TLRs in epithelial and interstial cells could be one of the links between exogenous/endogenous noxious signals and amplification of immune and fibroproliferative responses.…”

Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes

“…There are also some studies that relate IPF risk, microbiome diversity, host defense pathways ( MUC5B , ATP11A , TOLLIP ), and disease progression [25,26].…”