Highlights
- •Loss of lung function during late childhood remains a problem for patients with cystic fibrosis.
- •Respiratory exacerbations requiring hospitalization in early life appear to me drivers of loss of lung function later in childhood.
- •In this study we confirm that respiratory exacerbations requiring hospitalization in the first 5 years of life, together with markers of neutrophilic inflammation drive loss of lung function from childhood to adolescence.
Abstract
Background
Despite improvements in general health and life expectancy in people with cystic fibrosis
(CF), lung function decline continues unabated during adolescence and early adult
life.
Methods
We examined factors present at age 5-years that predicted lung function decline from
childhood to adolescence in a longitudinal study of Australasian children with CF
followed from 1999 to 2017.
Results
Lung function trajectories were calculated for 119 children with CF from childhood
(median 5.0 [25%-75%=5.0–5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4–13.8]
years). Lung function fell progressively, with mean (standard deviation) annual change
-0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC
Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence,
in multivariable analyses, were hospitalisation for respiratory exacerbations in the
first 5-years of life (FEV1/FVC p = 0.001, FEF25–75 p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1 p = 0.05, FEF25–75 p = 0.02). No examined factor predicted a decline in the FVC Z-score.
Conclusions
Action in the first 5-years of life to prevent and/or treat respiratory exacerbations
and counteract neutrophilic inflammation in the lower airways may reduce lung function
decline in children with CF, and these should be targets of future research.
Keywords
Abbreviations:
ACFBAL (Australasian cystic fibrosis bronchoalveolar lavage), CF-FAB (longitudinal observational follow-up study of the ACFBAL cohort)To read this article in full you will need to make a payment
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References
Ahern S., Salimi F., Caruso M., Ruseckate R., Bell S., Burke N., et al. The ACFDR Annual Report 2020. Melbourne: department of epidemiology and preventative medicine; 2021. Report No 22.
Cystic fibrosis foundation. Cystic fibrosis foundation patient registry. Bethesda, Maryland; 2019.
- Early lung disease in infants and preschool children with cystic fibrosis. What have we learned and what should we do about it?.Am J Respir Crit Care Med. 2017; 195: 1567-1575
- Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis.Thorax. 2011; 66: 408-413
- Inflammatory responses to individual microorganisms in the lungs of children with cystic fibrosis.Clin Infect Dis. 2011; 53: 425-432
- Risk factors for bronchiectasis in children with cystic fibrosis.N Engl J Med. 2013; 368: 1963-1970
- Diagnosis and early life risk factors for bronchiectasis in cystic fibrosis: a review.Expert Rev Respir Med. 2016; 10: 1003-1010
- Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.Am J Respir Crit Care Med. 2014; 190: 1111-1116
- The association between Staphylococcus aureus and subsequent bronchiectasis in children with cystic fibrosis.J Cystic Fibrosis. 2018; 17: 462-469
- Aspergillus infections and progression of structural lung disease in children with cystic fibrosis.Am J Respir Crit Care Med. 2020; 201: 688-696
- Aspergillus and progression of lung disease in children with cystic fibrosis.Thorax. 2019; 74: 125-131
- Total bacterial load, inflammation, and structural lung disease in paediatric cystic fibrosis.J Cystic Fibrosis. 2020; 19: 923-930
- Forced expiratory volume in 1 second variability helps identify patients with cystic fibrosis at risk of greater loss of lung function.J Pediatr. 2016; 169 (116-21.e2)
- Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening.J Pediatr. 2009; 155: 623-628
- Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial.J Am Med Assoc. 2011; 306: 163-171
- Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age.Thorax. 2013; 68: 643-651
- Hennig S. Pseudomonas aeruginosa eradication therapy and risk of acquiring Aspergillus in young children with cystic fibrosis.Thorax. 2019; 74: 740-748
- Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.Eur Respir J. 2012; 40: 1324-1343
- Lung function, bronchial responsiveness, and asthma in a community cohort of 6-year-old children.Am J Respir Crit Care Med. 2004; 169: 850-854
- A class of linear spectral models and analyses for the study of longitudinal data.Biometrics. 1989; 45: 831-849
- Bayesian Model Selection in Social Research.Sociological Methodology. 1995; 25: 111-163
- Risk factors for lung function decline in a large cohort of young cystic fibrosis patients.Pediatr Pulmonol. 2015; 50: 763-770
- Relationship of Antibiotic Treatment to Recovery after Acute FEV1 Decline in Children with Cystic Fibrosis.Ann Am Thor Soc. 2017; 14: 937-942
- Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.J Pediatr. 2013; 163 (1152-7.e2)
- The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis.Eur Respir J. 2019; 54
- Oxidative stress and abnormal bioactive lipids in early cystic fibrosis lung disease.J Cystic Fibrosis. 2019; 18: 781-789
- Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis.Am J Respir Crit Care Med. 2012; 186: 857-865
- Ivacaftor in infants aged 4 to <12 months with cystic fibrosis and a gating mutation. Results of a two-part phase 3 clinical trial.Am J Respir Crit Care Med. 2021; 203: 585-593
- Targeting cystic fibrosis inflammation in the age of CFTR modulators: focus on macrophages.Eur Respir J. 2021; 572003502
- Aspergillus colonization and antifungal immunity in cystic fibrosis patients.Med Mycol. 2019; 57: S118-Ss26
- Longitudinal analysis of lung function growth in healthy children and adolescents.J Appl Physiol. 1991; 70: 770-777
Article info
Publication history
Published online: March 24, 2022
Accepted:
March 20,
2022
Received in revised form:
March 7,
2022
Received:
November 25,
2021
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
