Variability of lung clearance index in clinically stable cystic fibrosis lung disease in school age children

Background

Data on long term variability of Lung Clearance Index (LCI) in Cystic Fibrosis (CF) is urgently needed to guide test result interpretation. Our aim was to evaluate LCI variability in clinically stable CF lung disease in school age children.

Effect of posture on lung ventilation distribution and associations with structure in children with cystic fibrosis

Background

We assessed the effect of posture on ventilation distribution and the impact on associations with structural lung disease.

Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth

Background

Lung impairment in cystic fibrosis (CF) starts in infancy. However, tools to monitor early lung disease are limited. Respiratory rate (RR) as a key vital sign is easy to assess during sleep and is elevated during acute respiratory disease. Thus, elevated RR could indicate early lung impairment and potentially serve as a diagnostic tool in disease monitoring.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF.Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases.We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.     

Variability of monthly nitrogen multiple-breath washout during one year in children with cystic fibrosis

Background

Knowledge of between-session variability of nitrogen multiple-breath washout (N₂MBW) indices is crucial when designing longitudinal interventional studies and in disease monitoring using N₂MBW as end-point. Such information is currently sparse.

Impaired peripheral airway function in adults following repair of esophageal atresia

Background

Esophageal atresia (EA) often leads to persistent symptoms and impaired respiratory function in adulthood. The role of peripheral airways in this impairment has not been previously investigated. Furthermore, asthma-like symptoms are common in these patients.

Purpose

The purpose of this study was to investigate pulmonary outcome, including possible peripheral airway dysfunction, perhaps missed by conventional pulmonary function tests and to see if the diagnosis asthma was accurate.

Methods

Twenty eight patients operated for EA in Gothenburg 1968–1983 answered a questionnaire regarding respiratory symptoms and underwent pulmonary function tests. Peripheral airway function was measured by multiple breath washout.

Results

22/28 (79%) patients had a history of respiratory symptoms. Abnormal peripheral airway function was found in 17 (61%) patients, while only 6 (21%) patients displayed values indicating central obstruction. Nine patients had restrictive disease. Airway hyperresponsiveness was frequent and associated with atopy and airway inflammation. However, respiratory symptoms or doctor-diagnosed asthma did not correlate with any specific lung function test abnormality.

Conclusion

Different lung function abnormalities are present in EA survivors, and peripheral airway disease is common. Classical asthma seems to be difficult to diagnose in this patient group. Given the high prevalence of respiratory morbidity, long-term follow-up of pulmonary function, including peripheral airway function, is warranted.     

Comparison of lung clearance index determined by washout of N2 and SF6 in infants and preschool children with cystic fibrosis

BackgroundMultiple-breath washout (MBW) has been shown to detect early impairment of lung function in children with cystic fibrosis (CF). Nitrogen (N₂) or sulfur hexafluoride (SF₆) can be used as tracer gas for MBW. Recent data indicated higher lung clearance index (LCI) values measured with N₂-MBW than concurrent SF₆-MBW in older children and adults, however, a comparison in infants and younger children, as well as to other outcome measures of CF lung disease is pending.MethodsN₂- and SF₆-MBW were performed consecutively in 31 sedated infants and preschool children with CF (mean age, 2.3 ± 0.8 years) and 20 controls (mean age, 2.3 ± 1.1 years) using the Exhalyzer D system. Children with CF also underwent chest magnetic resonance imaging (MRI).ResultsMean difference (95% CI) in LCI between N₂- and SF₆-MBW was 1.1 ± 0.4 (0.9 to 1.3) in controls and 2.1 ± 1.9 (1.4 to 2.8) in CF. Agreement between N₂- and SF₆-LCI was poor in children with CF. N₂-LCI and SF₆-LCI correlated with MRI, however N₂-LCI showed a higher concordance with MRI than SF₆-LCI. The absolute difference between N₂- and SF₆-LCI values increased with the severity of CF lung disease as determined by MRI scores.ConclusionN₂-LCI values were higher than SF₆-LCI values in infants and preschool children with CF and controls. Better concordance of N₂-LCI than SF₆-LCI with chest MRI scores point towards of a higher sensitivity of N₂-LCI to detect early lung disease in children with CF.     

Club cell secretory protein and lung function in children with cystic fibrosis

BackgroundClub cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF).MethodsWe used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV₁ levels in adolescence (LLF and HLF groups, respectively; N = 130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV₁ and FEV₁/FVC% predicted levels between ages 7–16 using mixed models.ResultsCompared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV₁/FVC and, marginally, FEV₁ (p = 0.003 and 0.025, respectively; N = 611 participants, 20,801 lung function observations).ConclusionsSerum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.     

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis

Background

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown.

The association between Staphylococcus aureus and subsequent bronchiectasis in children with cystic fibrosis

Background

Staphylococcus aureus (S. aureus) may be related to more rapid progression of cystic fibrosis (CF) lung disease.

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

BACKGROUND: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple-breath 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 (FEV(0.5) and FEF(25-75 )) than boys (mean (95% CI girls-boys): -1.2 (-2.1 to -0.3) for FEV(0.5) Z score; FEF(25-75): -1.2 (-2.2 to -0.15)). 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.     

A contemporary evaluation of pulmonary function in children undergoing lung resection in infancy

Background/Purpose

The management of asymptomatic congenital lung lesions is controversial. Some centers recommend resection in infancy, and others prefer observation. Our objective was to evaluate the pulmonary function of children who underwent lung resection at 12 months or younger. We hypothesized that these children would not have a significant reduction in pulmonary function when compared with norms for age.

Methods

All patients at 2 tertiary-care children's hospitals who underwent lung resection at 12 months or younger and are currently older than 5 years were identified and prospectively recruited. Pulmonary function testing was standardized in all patients.

Results

Fourteen children were tested prospectively, whereas results were available for another 5 children. Four children were excluded for inability to perform pulmonary function testing (n = 2) or for preexisting pulmonary hypoplasia/syndrome (n = 2). Pulmonary function testing values were considered normal if they were more than 80% of predicted. Forced vital capacity was normal in 14 (93%) of 15 children, and forced expiratory volume in 1 second was normal in 13 (86%) of 15 children. Diffusion capacity and respiratory muscle strength were normal in all children tested.

Conclusions

Most children undergoing lung resection in infancy will have normal pulmonary function tests, supporting our philosophy of early, elective resection of congenital lung lesions.     

Radionuclide imaging study of long-term pulmonary function after lobectomy in children with congenital cystic lung disease

Purpose

We evaluated the long-term pulmonary function after lobectomy for congenital cystic lung disease, in both infants and children, using radionuclide imaging (RI).

Methods

We performed a retrospective review of 93 patients who underwent resection of cystic lung lesions between 1974 and 2001. The results of postoperative lung volume/perfusion scintigraphy at 1 (n = 64), 5 (n = 32), and 10 years (n = 18) after surgery (V1, 5, 10/Q1, 5, 10) and mean transit time (MTT—a marker for air-trapping) at 1, 5, and 10 years after surgery (MTT1, 5, 10) were compared with respect to age at operation, preoperative infection, underlying disease, and type of surgery.

Results

Patients who were younger than 1 year at the time of surgery showed a significantly lower MTT5 (1.09 ± 0.08) and MTT10 (1.15 ± 0.11) than patients who were older than 1 year at the time of surgery (MTT5, 1.49 ± 0.67; MTT10, 1.54 ± 0.33). The noninfected group had significantly higher Q10 and lower MTT10 values (P < .05) compared to the infected group. No significant differences were observed between patients with single lobe vs multiple lobe resection.

Conclusions

The optimal age for surgery in patients with congenital cystic lung disease appears to be less than 1 year.     

Pulmonary exacerbations and acute declines in lung function in patients with cystic fibrosis

Background

Patients with cystic fibrosis (CF) who experience acute declines in percent predicted FEV₁ (ppFEV₁ decreased ≥10% relative to baseline) are often not treated with antibiotics for pulmonary exacerbations (PEx), whereas other patients are treated even when they have not experienced a decline in lung function.

Determining presence of lung disease in young children with cystic fibrosis: lung clearance index, oxygen saturation and cough frequency

BackgroundAccurate assessment of pulmonary status in young children with cystic fibrosis (CF) requires sensitive and objective monitoring techniques.ObjectivesThis study aimed to evaluate the feasibility of lung clearance index (LCI) calculated from multiple breath washout (MBW), home nocturnal pulse oximetry and home nocturnal cough recording in young children with CF, and determine whether these tests can distinguish CF patients from healthy controls.MethodsWe performed a prospective cross-sectional study in 20 CF patients and 30 healthy children aged 0–4 years. MBW was performed in awake and unsedated children at the outpatient clinic using a commercially available device. Measurements of nocturnal oxygen saturation and nocturnal cough were done at home using a pulse oximeter and an audiometer.ResultsThere was a significant difference in mean LCI between healthy children and CF patients (LCI 7.1 vs. 9.3, p < 0.001). Nocturnal oxygen saturation was normal in both groups and did not significantly differ between the groups. Similarly, cough showed no differences between both groups. Cough varied widely between children and between nights. Success rates for saturation and cough measurements were 90% and were similar for CF patients and healthy children. Success rate for LCI was 75% for CF patients and 50% for healthy children.ConclusionsMeasurements of LCI, nocturnal oxygen saturation and cough were feasible in young children; however LCI was the only variable that showed a significant difference between children with CF and healthy children.