Lung function testing in infants with cystic fibrosis: Lessons from the past and future directions

Gappa, Monika; Ranganathan, Sarath; Stocks, Janet

doi:10.1002/ppul.1113

Cited by 65 publications

(35 citation statements)

References 87 publications

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“…Relationship with previous studies of lung function in infants and young children with cystic fibrosis Despite the popularity of the tidal rapid thoracic compression technique, [36][37][38] recent studies have suggested that the raised volume technique is a more sensitive means of identifying diminished airway function in infants with cystic fibrosis. 11 12 There is now clear evidence that the MBW technique detects abnormal lung function more readily in both preschool and school age children with cystic fibrosis than spirometry, 1 13 15 but this does not seem to be the case during infancy.…”

Section: Strengths and Limitationsmentioning

confidence: 87%

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

Lum¹,

Gustafsson

Ljungberg³

et al. 2007

Thorax

199

211

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Background: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiplebreath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives: To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco-abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods: Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results: Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow-volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume ) than boys (mean (95% CI girls-boys): -1.2 (-2.1 to 20.3) for FEV 0.5 Z score; FEF 25-75 : -1.2 (-2.2 to 20.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions: These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC.

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Section: Strengths and Limitationsmentioning

confidence: 87%

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

Lum¹,

Gustafsson

Ljungberg³

et al. 2007

Thorax

199

211

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“…The utility of lung function studies to detect early abnormalities in infants with CF have been previously reviewed [59]. The RVRTC technique can identify diminished lung function in infants diagnosed both clinically [60] and by newborn screening [61].…”

Section: Infant Lung Functionmentioning

confidence: 99%

“…There have been a few intervention studies in CF that have used infant lung function as an outcome [59]. The RVRTC technique has been used in two safety studies of hypertonic saline to demonstrate acute tolerability [19,20,66,67].…”

Section: Infant Lung Functionmentioning

confidence: 99%

Early intervention studies in infants and preschool children with cystic fibrosis: are we ready?

et al. 2013

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Cystic fibrosis (CF) lung disease starts early in life and progresses even in the absence of clinical symptoms. Therefore, sensitive outcome measures to quantify and track these early abnormalities in infants and young children are needed; both for clinical care and interventional trials. Currently, the efficacy of most therapeutic interventions in CF has not been tested in children under the age of 6 years and drug development programmes have focused on assessing safety rather than efficacy in this age group. This article summarises the current status for outcome measures that can be utilised in clinical trials in infants and children with CF. Two methodologies are specifically highlighted in this review; chest computed tomography to assess structural damage of the lung and multiple breath washout as a technique to quantify ventilation inhomogeneity. While not all questions regarding the utility of these outcome measures in infants and young children have been resolved, significant advances have been made and it now appears feasible to design and conduct adequately powered efficacy studies in this age group. This could be a crucial step to further improve outcomes in CF patients as initiating effective treatment early is considered essential to prevent permanent lung damage. @ERSpublications Crucial to CF outcome is early effective treatment, hence intervention studies in infants and preschool children are a must

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“…This study in minimally symptomatic infants suggested that the early structural airway changes led to bronchiectasis and that chronic infection might be a secondary contributor to airway remodeling. Newer, sensitive pulmonary function studies also reported diminished airway function in infants soon after diagnosis with CF (Gappa et al, 2001). Many of these infants had no history of prior clinical infection.…”

Section: Introductionmentioning

confidence: 99%

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Cohen

Larson

2006

Developmental Dynamics

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There is growing evidence for the role of CFTR (cystic fibrosis transmembrane conductance regulator) in lung development and differentiation. The mechanism by which the chloride channel could affect lung organogenesis, however, is unknown. In utero CFTR gene transfer in the fetal lungs of mice, rats, and non-human primates was shown previously to alter lung structure and function. A study of the genes altered in the fetal rat lung following CFTR overexpression was initiated in an effort to determine the molecular mechanism for CFTR-dependent differentiation. In utero gene transfer with recombinant adenoviruses carrying either a reporter gene or CFTR resulted in the increased expression of a number of genes upon microarray analysis. The majority of the genes overexpressed in the CFTR-treated lungs were primarily associated with muscle structure and function. Histological and biochemical characterization of these proteins including myosin heavy chain, heat shock protein 27, and isoforms of myosin light chain showed that CFTR overexpression had a profound effect on smooth muscle contraction-related proteins. The CFTR-dependent regulation of smooth muscle contraction related proteins was shown to be related to chloride and extracellular ATP and was dependent upon the PI3 Kinase and Phospholipase C pathways. The changes in smooth muscle proteins were consistent with CFTR-dependent contractions of the embryonic airway smooth muscle. An assay was developed using fluorescent polystyrene beads to show that CFTR did indeed increase amniotic fluid flow into the fetal lung. Increased amniotic fluid pressure was shown previously to be associated with stretch-induced differentiation of the lung. Evaluation of neonatal respiratory function showed that CFTR-dependent muscle contractions and increased amniotic fluid pressure resulted in accelerated maturation of the neonatal rat lung. In addition, these CFTR-dependent changes were shown to be sufficient to reverse the lung phenotype of the CFTR knockout mouse. Mechanical forces influence lung development through pulmonary distension. CFTR overexpression in the fetal lung altered differentiation and development in the lung. These results are consistent with CFTR influencing lung development by regulating the muscle contractions associated with cytoskeletal tension and stretch induced differentiation. Deficiency of CFTR altering lung development would contribute significantly to the Cystic Fibrosis disease phenotype.

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Lung function testing in infants with cystic fibrosis: Lessons from the past and future directions

Cited by 65 publications

References 87 publications

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

Early intervention studies in infants and preschool children with cystic fibrosis: are we ready?

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

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