Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis

Waters, Valerie; Stanojevic, Sanja; Atenafu, Eshetu G.; Lu, Annie; Yau, Yvonne; Tullis, Elizabeth; Ratjen, Félix

doi:10.1183/09031936.00159111

Cited by 216 publications

(177 citation statements)

References 25 publications

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“…This finding is not surprising, as many CF deaths are preceded by worsening infection; however, minimising these events is critical, as the rate of decline in FEV1 is greatest when exacerbations occurs frequently and within a short time frame [26]. Malnutrition continues to be an important risk factor for death.…”

Section: Discussionmentioning

confidence: 96%

A contemporary survival analysis of individuals with cystic fibrosis: a cohort study

et al. 2014

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Previously established predictors of survival may no longer apply in the current era of cystic fibrosis (CF) care. Our objective was to identify risk factors associated with survival in a contemporary CF population.We used the Canadian CF Registry, a population-based cohort, to calculate median age of survival and summarise patient characteristics from 1990 to 2012. Clinical, demographic and geographical factors, and survival were estimated for a contemporary cohort (2000-2012) using Cox proportional hazards models.There were 5787 individuals in the registry between 1990 and 2012. Median survival age increased from 31.9 years (95% CI 28.3-35.2 years) in 1990 to 49.7 years (95% CI 46.1-52.2 years) in the most current 5-year window ending in 2012. Median forced expiratory volume in 1 s improved ( p=0.04) and fewer subjects were malnourished ( p<0.001) over time. Malnourished patients (hazard ratio (HR) 2.1, 95% CI 1.6-2.8), those with multiple exacerbations (HR 4.5, 95% CI 3.2-6.4) and women with CF-related diabetes (HR 1.8, 95% CI 1.2-2.7) were at increased risk of death.Life expectancy in Canadians with CF is increasing. Modifiable risk factors such as malnutrition and pulmonary exacerbations are associated with an increased risk of death. The sex gap in CF survival may be explained by an increased hazard for death in women with CF-related diabetes. @ERSpublications Malnutrition and pulmonary exacerbations increase the risk of death in CF but survival in CF has increased over time

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Section: Discussionmentioning

confidence: 96%

A contemporary survival analysis of individuals with cystic fibrosis: a cohort study

et al. 2014

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“…In a study of asthmatics over a period of 11 years, a relationship was seen between exacerbation frequency and FEV1 decline [8]. In a Canadian study, WATERS et al [9] showed that severe cystic fibrosis exacerbations (requiring hospitalisation) were associated with greater FEV1 decline. Although the European Cystic Fibrosis Society study did not report on exacerbations they have reported a link between chronic Pseudomonas aeruginosa infection (a known risk factor for cystic fibrosis exacerbations) and FEV1 decline [10], from which such a relationship may be inferred and this supports the findings of the Canadian study.…”

Section: @Erspublicationsmentioning

confidence: 99%

Exacerbation frequency and FEV1 decline of COPD: is it geographic?

Seemungal

Wedzicha

2014

European Respiratory Journal

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@ERSpublicationsAll exacerbation data, whether reported, self-managed or untreated, is required to recognise health burdens in COPD http://ow.ly/usGyB Chronic obstructive pulmonary disease (COPD) exacerbations are episodes of symptom worsening that have major impacts on a variety of health outcomes, including quality of life, hospital admission and death [1]. Exacerbation reduction is now a key outcome for pharmacological therapies in COPD and, thus, if exacerbation can be prevented how does this affect disease progression and lung function decline?The issue of the importance of lung function decline in COPD first arose when FLETCHER and PETO [2] explored lung function in a cohort of 792 male British postal workers. These subjects were studied over 8 years and it was found that exacerbations were associated with the ratio of forced expiratory volume in 1 s (FEV1) to the cube of the height, although the exacerbation definition was limited at that time. This work was followed in close succession by a study from Utah in which KANNER et al. [3] showed that exacerbation frequency was related to COPD severity, thus implicating exacerbation frequency as a factor in FEV1 decline. However, detecting the relationship proved elusive until the Lung Health Study showed that in smokers and intermittent quitters each additional exacerbation reported to physicians caused a greater annual decline of 7 mL [4]. The following year, the London COPD cohort study reported that in patients with a history of more frequent exacerbations there was an increased rate of decline of 8 mL per year compared with infrequent exacerbators [5]. The relationship between exacerbation frequency and FEV1 decline in COPD has also been seen in the UPLIFT study [6] and another study from Greece [7]. All of these studies were performed on European or North American subjects with COPD.In diseases other than COPD, an occasional relationship has been reported between exacerbation rates and FEV1 decline. In a study of asthmatics over a period of 11 years, a relationship was seen between exacerbation frequency and FEV1 decline [8]. In a Canadian study, WATERS et al. [9] showed that severe cystic fibrosis exacerbations (requiring hospitalisation) were associated with greater FEV1 decline. Although the European Cystic Fibrosis Society study did not report on exacerbations they have reported a link between chronic Pseudomonas aeruginosa infection (a known risk factor for cystic fibrosis exacerbations) and FEV1 decline [10], from which such a relationship may be inferred and this supports the findings of the Canadian study.In this issue of the European Respiratory Journal, the relationship between exacerbations and lung function decline is addressed in a cohort of 279 Japanese subjects followed over a 5-year period in Hokkaido [11]. The detection rate for exacerbations in this study was 0.78 events per year using a symptom-based definition. The study found no significant relation between exacerbation rate and FEV1 decline. The annual decline in FEV1 in the Hokkaido...

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“…Without intervention, this situation gradually deteriorates causing plugging of small airways, bacterial infection, chronic local inflammation and eventually bronchiectasis [9,19,21]. Furthermore, repeated pulmonary exacerbations in CF have been shown to contribute to an accelerated decline in lung function [33].…”

Section: Review: Cftr Modulators In Cf N Derichsmentioning

confidence: 99%

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

Derichs

2013

European Respiratory Review

101

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Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.

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Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis

Cited by 216 publications

References 25 publications

A contemporary survival analysis of individuals with cystic fibrosis: a cohort study

A contemporary survival analysis of individuals with cystic fibrosis: a cohort study

Exacerbation frequency and FEV1 decline of COPD: is it geographic?

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

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