Cystic Fibrosis Lung Disease in the Aging Population

Abstract

The demographics of the population with cystic fibrosis (CF) is continuously changing, with nowadays adults outnumbering children and a median predicted survival of over 40 years. This leads to the challenge of treating an aging CF population, while previous research has largely focused on pediatric and adolescent patients. Chronic inflammation is not only a hallmark of CF lung disease, but also of the aging process. However, very little is known about the effects of an accelerated aging pathology in CF lungs. Several chronic lung disease pathologies show signs of chronic inflammation with accelerated aging, also termed “inflammaging”; the most notable being chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In these disease entities, accelerated aging has been implicated in the pathogenesis via interference with tissue repair mechanisms, alterations of the immune system leading to impaired defense against pulmonary infections and induction of a chronic pro-inflammatory state. In addition, CF lungs have been shown to exhibit increased expression of senescence markers. Sustained airway inflammation also leads to the degradation and increased turnover of cystic fibrosis transmembrane regulator (CFTR). This further reduces CFTR function and may prevent the novel CFTR modulator therapies from developing their full efficacy. Therefore, novel therapies targeting aging processes in CF lungs could be promising. This review summarizes the current research on CF in an aging population focusing on accelerated aging in the context of chronic airway inflammation and therapy implications.

Role of pulmonary epithelial arginase‐II in activation of fibroblasts and lung inflammaging

“…First, Arg‐II but not Arg‐I (an enzyme involved in hepatic urea cycle) plays an important role in pulmonary inflammaging and fibrosis. Development of specific Arg‐II inhibitors is expected to have great potential to treat lung inflammaging and pulmonary fibrosis disease, particularly in women without risk of liver damage; second, given a key role of chronic inflammation in pulmonary fibrosis (Heukels et al, 2019 ; Kunzi et al, 2021 ) and that increased Arg‐II promotes inflammaging and fibrosis in other organs in aging (Huang et al, 2021 ; Yepuri et al, 2012 ), Arg‐II could be a therapeutic target in treatment of other organ fibrosis inaging, which may result in lifespan extension.…”

Health-Related Quality of Life in Adults with Cystic Fibrosis: Familial, Occupational, Social, and Mental Health Predictors

“…Age was negatively correlated with the “physical functioning”, “vitality”, and “health perception” domains. We can hypothesize that the occurrence of CF-related comorbidities overtime impact self-perception HRQoL [ 33 ]. However, age was not negatively correlated with the “treatment burden” domain in our study.…”

Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine

“…The mechanisms responsible for this effect are varied and involve different levels, including the reduced expression of CFTR transcription, the accelerated degradation of the protein and the alteration of the opening of the channel [17,33,34]. On the other hand, in cases of severe CFTR dysfunction, such as CF, an oxidative imbalance is described as leading to the increased production of reactive oxygen species [35]. If this double effect was demonstrated in COPD, this would lead to the consideration that oxidative stress not only played a central role in the pathogenesis, but had a clear therapeutic objective with which to break this possible redundant mechanism.…”