Risk Factors for Bronchiectasis in Children with Cystic Fibrosis

Sly, Peter D.; Gangell, Catherine; Chen, Linping; Ware, Robert S.; Ranganathan, Sarath; Mott, Lauren; Murray, Conor; Stick, Stephen M.

doi:10.1056/nejmoa1301725

Cited by 523 publications

(405 citation statements)

References 26 publications

Supporting

Mentioning

356

Contrasting

Unclassified

Order By: Relevance

“…However, controversy exists as to whether the targeting of innate immune pathways, by neutrophil recruitment and/or activation, represents a promising strategy in CF lung disease. On the one hand, there are clear relationships between neutrophil products, prototypical NE and decreased lung function [22] as well as bronchiectasis [2]. On the other hand, targeting excessive proteolytic activities in CF has clinically not been successful so far.…”

Section: Discussionmentioning

confidence: 99%

“…Cystic fibrosis (CF) lung disease, the most common inherited lethal disease in Caucasians [1], is characterized by an early [2], nonresolving [3] and harmful [3,4] activation of the innate immune system. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, mainly expressed at the apical membrane of epithelial cells [5].…”

Section: Cf Lung Diseasementioning

confidence: 99%

“…Studies from regions with CF newborn screening indicate that the innate immune system, as reflected prototypically by neutrophil products present in CF airway fluids, is operative in infants with CF and predicts the later outcome of irreversible pulmonary disease [2]. Based on these and other studies, innate immune cells have come into the focus of understanding and treating CF lung disease [3].…”

Section: Cf Lung Diseasementioning

confidence: 99%

“…The correlation between neutrophil activation and irreversible lung tissue remodeling (bronchiectasis) [2] suggests a harmful role, but without functional neutrophils (as exemplified in patients with the primary immunodeficiency chronic granulomatous disease), we cannot efficiently defend against bacteria and fungi. Consequently, dampening neutrophil activation would be reasonable, while completely abrogating neutrophil influx or function might be dangerous.…”

Section: Current Controversies In Innate Immunity Of Cf Lung Diseasementioning

confidence: 99%

See 3 more Smart Citations

Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease

et al. 2016

View full text Add to dashboard Cite

Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. The inflammatory response in CF is dominated by the activation of the innate immune system. Bacteria and fungi represent the key pathogens chronically colonizing the CF airways. In response, innate immune pattern recognition receptors, expressed by airway epithelial and myeloid cells, sense the microbial threat and release chemoattractants to recruit large numbers of neutrophils into CF airways. However, neutrophils fail to efficiently clear the invading pathogens, but instead release harmful proteases and oxidants and finally cause tissue injury. Here, we summarize and discuss current concepts and controversies in the field of innate immunity in CF lung disease, facing the ongoing questions of whether inflammation is good or bad in CF and how innate immune mechanisms could be harnessed therapeutically.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Cf Lung Diseasementioning

confidence: 99%

Section: Cf Lung Diseasementioning

confidence: 99%

Section: Current Controversies In Innate Immunity Of Cf Lung Diseasementioning

confidence: 99%

See 2 more Smart Citations

Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…It is recognised that bronchiectasis occurs early on in a person with CF [4] and progresses over time with associated decline in lung function, ultimately resulting in respiratory failure. Over 95% of morbidity and mortality arises from respiratory disease.…”

Section: Introductionmentioning

confidence: 99%

Inhaled Interventions in Cystic Fibrosis: Mucoactive and Antibiotic Therapies

Hurt¹,

Bilton²

2014

Respiration

View full text Add to dashboard Cite

Treatment of cystic fibrosis lung disease has developed from an understanding of the abnormal airway surface liquid resulting from a lack of function of the cystic fibrosis transmembrane regulator protein. Mucus plugging resulting in infection and inflammation leads to airway wall destruction and bronchiectasis. Inhaled therapies have formed the backbone of treatments. In combination with antibiotics delivered direct to the airway, mucoactive drugs, including mucolytics and hyperosmolar agents, are utilised to improve mucociliary clearance to reduce infection and inflammation. Until recently, airway therapies were delivered as nebulisers, but we have now entered the era of dry powder inhalers for treatment of cystic fibrosis lung disease. The theory and practice of these therapies are discussed in this review.

show abstract

Cystic Fibrosis

Ong

Ramsey

2023

JAMA

View full text Add to dashboard Cite

ImportanceCystic fibrosis, a genetic disorder defined by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affects more than 30 000 individuals in the US and approximately 89 000 worldwide. Absent or decreased function of the CFTR protein is associated with multiorgan dysfunction and shortened life expectancy.ObservationsCFTR is an anion channel in the apical membrane of epithelial cells. Loss of function leads to obstructed exocrine glands. Of people with cystic fibrosis in the US, approximately 85.5% have the gene variant F508del. Manifestations of cystic fibrosis in patients with the F508del gene variant begin in infancy with steatorrhea, poor weight gain, and respiratory symptoms (coughing, wheezing). As people with cystic fibrosis age, chronic respiratory bacterial infections cause loss of lung function and bronchiectasis. With the availability of universal newborn screening in multiple countries including the US, many people with cystic fibrosis are asymptomatic at diagnosis. With multidisciplinary care teams that included dietitians, respiratory therapists, and social workers, treatment of cystic fibrosis can slow disease progression. Median survival has improved from 36.3 years (95% CI, 35.1-37.9) in 2006 to 53.1 years (95% CI, 51.6-54.7) in 2021. Pulmonary therapies for patients with cystic fibrosis consist of mucolytics (eg, dornase alfa), anti-inflammatories (eg, azithromycin), and antibiotics (such as tobramycin delivered by a nebulizer). Four small molecular therapies, termed CFTR modulators, that facilitate CFTR production and/or function have received regulatory approval. Examples are ivacaftor and elexacaftor-tezacaftor-ivacaftor. For example, in patients with 1 F508del variant, the combination of ivacaftor, tezacaftor, and elexacaftor improved lung function from −0.2% in the placebo group to 13.6% (difference, 13.8%; 95% CI, 12.1%-15.4%) and decreased the annualized estimated rate of pulmonary exacerbations from 0.98 to 0.37 (rate ratio, 0.37; 95% CI, 0.25-0.55). Improved respiratory function and symptoms have lasted up to 144 weeks in postapproval observational studies. An additional 177 variants are eligible for treatment with the elexacaftor-tezacaftor-ivacaftor combination.ConclusionCystic fibrosis affects approximately 89 000 people worldwide and is associated with a spectrum of disease related to exocrine dysfunction, including chronic respiratory bacterial infections and reduced life expectancy. First-line pulmonary therapies consist of mucolytics, anti-inflammatories, and antibiotics, and approximately 90% of people with cystic fibrosis who are 2 years or older may benefit from a combination of ivacaftor, tezacaftor, and elexacaftor.

show abstract

Risk Factors for Bronchiectasis in Children with Cystic Fibrosis

Abstract: Neutrophil elastase activity in BAL fluid in early life was associated with early bronchiectasis in children with cystic fibrosis. (Funded by the National Health and Medical Research Council of Australia and Cystic Fibrosis Foundation Therapeutics.)

Cited by 523 publications

References 26 publications

Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease

Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease

Inhaled Interventions in Cystic Fibrosis: Mucoactive and Antibiotic Therapies

Cystic Fibrosis

Contact Info

Product

Resources

About