Hospital therapy improves exercise tolerance and lung function in cystic fibrosis

We studied the benefits of in-hospital therapy on exercise capacity and related these changes to improvements in lung function in 17 patients with cystic fibrosis (CF) of moderate to extreme severity, as defined by results of pulmonary function tests performed at admission and discharge. Tolerance and adaptations to exercise were assessed from measures of peak work capacity (PWC), peak heart rate (PHR), and peak ventilation (PVE) obtained during an incremental exercise test. Treatment lasted from nine to 18 days. All measures of lung function improved; there also were significant increases in PWC, PHR, PVE, and PHR/PWC. Exercise-induced arterial desaturation was less at discharge than at admission. The PWC of the most severely affected patients remained abnormally low, and their adaptations to exercise were abnormal at discharge. We concluded that intensive in-hospital therapy will significantly improve exercise tolerance and lung function in patients with CF with moderate to severe pulmonary dysfunction.     

The systematic evaluation of the chest radiograph in cystic fibrosis

In antero-posterior and lateral chest radiographs of patients with cystic fibrosis changes may be observed which reflect underlying lung abnormalities. Increases in lung volume can result in forward bowing of the sternum, diaphragmatic depression and spinal kyphosis. Parenchymal lung changes which are directly or indirectly a consequence of bronchiolar mucus plugging with infection, include mottled shadowing and ring shadowing. Prominence of bronchial line shadows is also commonly seen. Large shadows due to confluent consolidation or collapse may occur. This paper gives a technique for the systematic evaluation of these changes which are then represented in numerical ternis The method gives repeatable results. The information recorded facilitates comparison of chest radiographs with each other and the comparison of radiological features with clinical and physiological assessments.     

Serial lung function studies in cystic fibrosis in the first 5 years of life

Lung mechanics were studied in 8 infants with cystic fibrosis at 6 months of life and radiosotopic lung function was measured in 5 of them at 5 years of age. The children who were initially asymptomatic had normal lung mechanics in infancy but the 2 restudied later had abnormal radioisotopic lung function. The symptomatic children showed abnormalities in infancy and more marked changes later. It is concluded that the lungs in cystic fibrosis are probably normal initially and that damage occurs later even in the absence of symptoms.     

Early airway infection,inflammation, and lung function in cystic fibrosis

Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV_0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV_0.5 195 ml and 236 ml respectively). Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients.     

Relationship between clinical conditions, radiographic findings and pulmonary functions in patients with cystic fibrosis

Clinical and radiological findings, quantified by special scores, in 36 patients with cystic fibrosis are compared with lung function measurements, including the ratio of RV/TLC and FEV/VC and the arterial blood gases at rest and during exercise. Although respiratory function tests were found to correlate well with both the pulmonary finding score and the chest radiographic score, distinction of three severity groups was possible only by a vector calculation of the blood gases in PaO2-PaCO2-diagram, at rest and during exercise. Thus, measurements of pO2 and pCO2 at rest and on exercise appear to be a helpful adjuvant to routine spirometry for the individual appraisal of the degree of lung involvement, performance and care level.     

The relationship between chest radiographic scores and respiratory function tests in children with cystic fibrosis

Chestradiographic scores and respiratory function on 80 sets of results from 50 patients with Cystic Fibrosis were analysed. Chest radiographic scores were assessed independently using the method of Chrispin and Norman. Respiratory function tests were found to correlate well with the chest radiographic score, the best correlation being with the forced expiratory volume in 0.75 sec. to forced vital capacity ratio F.E.V.0.75/ F.V.C. (r=–0.674 n=80 p<0.001).     

Serial lung function studies in cystic fibrosis in the first 5 years of life.

Lung mechanics were studied in 8 infants with cystic fibrosis at 6 months of life and radiosotopic lung function was measured in 5 of them at 5 years of age. The children who were initially asymptomatic had normal lung mechanics in infancy but the 2 restudied later had abnormal radioisotopic lung function. The symptomatic children showed abnormalities in infancy and more marked changes later. It is concluded that the lungs in cystic fibrosis are probably normal initially and that damage occurs later even in the absence of symptoms.     

Passive smoking and impaired lung function in cystic fibrosis

Passive smoking was measured in 57 children with cystic fibrosis and in 51 controls using a questionnaire and a measurement of urinary cotinine concentration. In the cystic fibrosis group, cotinine was significantly lower than in the controls. Also in this group, when the parents smoked the child's forced expiratory volume in one second decreased by 4% and the forced vital capacity by 3% for every 10 cigarettes smoked in the household each day.     

Early airway infection, inflammation, and lung function in cystic fibrosis.

AIMS: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). METHODS: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. RESULTS: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV(0.5) compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV(0.5) 195 ml and 236 ml respectively). CONCLUSIONS: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients.     

Growth and lung function in Asian patients with cystic fibrosis

Background: The incidence of cystic fibrosis (CF) in Asians is rare. How these patients fare in terms of morbidity and mortality in the UK compared to their non-Asian peers is not well documented. Aims: To retrospectively study annual reviews of 31 Asian CF patients from three London paediatric CF centres. Methods: Disease severity was assessed by lung function, age at first infection with Pseudomonas aeruginosa, and body mass index (BMI). The Asian children were compared with 143 matched non-Asian patients with CF. Matching criteria used were same sex and treatment centre as the Asian index patient. In addition, the controls were matched so that their date of birth, date of diagnosis, and date at annual review were within 12 months of the index patient. Results: There was no significant difference in age at diagnosis or age at annual review between the Asian and non-Asian children. Mean Z-scores for FEV₁ and FVC were significantly lower for the Asian girls. There was no significant difference in Z-scores for BMI between the Asian children and their controls. Age at first isolation of Pseudomonas aeruginosa in Asian girls was significantly later than for their controls (8.3 years compared to 5.6 years for non-Asian girls). Conclusions: While the Asian boys'' lung function seems comparable with that of their non-Asian peers, the Asian girls emerge as a potentially vulnerable group and more work is required to discover why this is the case.     

Passive smoking and impaired lung function in cystic fibrosis.

Passive smoking was measured in 57 children with cystic fibrosis and in 51 controls using a questionnaire and a measurement of urinary cotinine concentration. In the cystic fibrosis group, cotinine was significantly lower than in the controls. Also in this group, when the parents smoked the child's forced expiratory volume in one second decreased by 4% and the forced vital capacity by 3% for every 10 cigarettes smoked in the household each day.     

Structural lung changes,lung function,and non‐invasive inflammatory markers in cystic fibrosis

Robroeks CMHHT, Roozeboom MH, de Jong PA, Tiddens HAWM, Jöbsis Q, Hendriks HJ, Yntema J‐BL, Brackel HL, van Gent R, Robben S, Dompeling E. Structural lung changes, lung function, and non‐invasive inflammatory markers in cystic fibrosis.
Pediatr Allergy Immunol 2010: 21: 493–500.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard Cystic fibrosis (CF) lung disease is characterized by chronic airway inflammation and recurrent infections, resulting in (ir)reversible structural lung changes and a progressive decline in lung function. The objective of this study was to investigate the relationship between non‐invasive inflammatory markers (IM) in exhaled breath condensate (EBC), lung function indices and structural lung changes, visualized by high resolution computed tomography (HRCT) scans in CF. In 34 CF patients, lung function indices (forced expiratory volume in 1 s, forced vital capacity [FVC], residual volume, and total lung capacity [TLC]) and non‐invasive IM (exhaled nitric oxide, and condensate acidity, nitrate, nitrite, 8‐isoprostane, hydrogen peroxide, interferon‐gamma) were assessed. HRCT scans were scored in a standardized and validated way, a composite score and component scores were calculated. In general, the correlations between non‐invasive IM and structural lung changes, and between IM and lung function were low (correlation coefficients <0.40). Patients with positive sputum Pseudomonas cultures had higher EBC nitrite levels and higher parenchymal HRCT subscores than patients with Pseudomonas‐negative cultures (p < 0.05). Multiple linear regression models demonstrated that FVC was significantly predicted by hydrogen peroxide in EBC, and the scores of bronchiectasis and mosaic perfusion (Pearson correlation coefficient R = 0.78, p < 0.001). TLC was significantly predicted by 8‐isoprostane, nitrate, hydrogen peroxide in EBC, and the mucous plugging subscore (R = 0.92, p < 0.01). Static and dynamic lung function indices in this CF group were predicted by the combination of non‐invasive IM in EBC and structural lung changes on HRCT imaging. Future longitudinal studies should reveal whether non‐invasive monitoring of airway inflammation in CF adds to better follow‐up of patients.     

Growth and lung function in Asian patients with cystic fibrosis.

BACKGROUND: The incidence of cystic fibrosis (CF) in Asians is rare. How these patients fare in terms of morbidity and mortality in the UK compared to their non-Asian peers is not well documented. AIMS: To retrospectively study annual reviews of 31 Asian CF patients from three London paediatric CF centres. METHODS: Disease severity was assessed by lung function, age at first infection with Pseudomonas aeruginosa, and body mass index (BMI). The Asian children were compared with 143 matched non-Asian patients with CF. Matching criteria used were same sex and treatment centre as the Asian index patient. In addition, the controls were matched so that their date of birth, date of diagnosis, and date at annual review were within 12 months of the index patient. RESULTS: There was no significant difference in age at diagnosis or age at annual review between the Asian and non-Asian children. Mean Z-scores for FEV1 and FVC were significantly lower for the Asian girls. There was no significant difference in Z-scores for BMI between the Asian children and their controls. Age at first isolation of Pseudomonas aeruginosa in Asian girls was significantly later than for their controls (8.3 years compared to 5.6 years for non-Asian girls). CONCLUSIONS: While the Asian boys' lung function seems comparable with that of their non-Asian peers, the Asian girls emerge as a potentially vulnerable group and more work is required to discover why this is the case.     

Relationship between disease severity and inflammatory markers in cystic fibrosis

To evaluate the clinical use of measuring neutrophil, lymphocyte, and eosinophil activities, serum myeloperoxidase (MPO), soluble interleukin-2 receptors (sIL-2R), and eosinophil cationic protein (ECP) were measured in 98 patients with cystic fibrosis and in 85 healthy children. Serum concentrations of MPO, sIL-2R, and ECP were increased in patients with cystic fibrosis (median 807 micrograms/l, 4452 pg/ml, 48.8 micrograms/l, respectively) compared with the controls (median 319 micrograms/l, 2743 pg/ml, 9.4 micrograms/l). ECP concentrations, but not serum MPO or sIL-2R, were significantly related to disease severity assessed by the Shwachman-Kulczycki score and by pulmonary function (forced expiratory volume in one second % predicted). Neither ECP nor sIL-2R was influenced by Pseudomonas aeruginosa infection, acute pulmonary exacerbation, or atopy. Serum MPO, however, was strongly correlated with acute pulmonary exacerbation. In the light of these findings the measurement of serum ECP might thus be used for clinical monitoring and for assessing disease severity in cystic fibrosis. The measurement of serum MPO and sIL-2R did not correlate with the disease severity.     

Carbohydrate tolerance in cystic fibrosis is closely linked to pancreatic exocrine function

We evaluated carbohydrate tolerance in nine thin cystic fibrosis (CF) patients and in six controls, measuring responsiveness to the following insulinotropic secretagogues: oral glucose, IV glucose, and IV tolbutamide. Glucose responses segregated patients into two groups: Group I with normal carbohydrate tolerance associated with normal to slightly increased insulin responses, and Group II with impaired carbohydrate tolerance associated with insulinopenia. This latter group included one patient with frank diabetes. The CF patients demonstrated a significant positive correlation between insulin secretion, in response to each secretagogue, and pancreatic exocrine function as measured by serum pancreatic amylase isoenzyme concentration. Pancreatic alpha-cell function, as reflected by basal plasma glucagon concentrations, also correlated well with exocrine function in the CF patients, excluding the diabetic individual. The enteroinsular axis of the CF group was intact as reflected by normal plasma gastric inhibitory polypeptide concentrations in Group I and by elevated levels, basally and in response to oral glucose, in the insulinopenic Group II patients. Furthermore, those patients with impaired tolerance demonstrated a greater magnitude of insulinopenia compared to controls following IV glucose and possibly IV tolbutamide, than following oral glucose. Thus, these data suggest that loss of carbohydrate tolerance in patients with CF, like that seen with classical chronic pancreatitis, 1) parallels the loss of exocrine function, 2) is associated with appropriate enteroinsular signaling, and 3) can be detected earlier or more easily following testing with direct IV secretagogues than following oral glucose stimulation.     

Early detection of lung disease in children with cystic fibrosis using lung function

Measurement of lung function is routine in older children and adults with cystic fibrosis (CF) but not in infants and preschool children. Pulmonary infection, neutrophil-dominated inflammation and clinical exacerbations in young children similar to those seen in older subjects have been identified and highlight the urgent need to evaluate lung function in early life. Mounting evidence suggests lung function techniques sensitive to changes in peripheral lung function may be required to detect the early functional abnormalities in infants and preschool children with CF. In addition, the majority of studies in young children with CF have not reported longitudinal data and therefore the prognostic potential of existing lung function methods to track disease progression is poorly understood. This review aims to describe recent research findings in infants and preschool children and to outline currently available lung function techniques, issues around their standardization and their relative advantages and disadvantages in young children with CF.     

Relationship between impulse oscillometry and spirometric indices in cystic fibrosis children

Background: The aim of our retrospective study was to determine the relationship between impulse oscillometry ( IOS) data and spirometric tests in cystic fibrosis (CF) children.
Methods : Thirty CF children aged 4–19 years have performed lung function tests (LFT). A subset of 15 patients repeated LFT on five separate occasions. IOS parameters were respiratory resistance (Rrs), reactance (Xrs) and impedance at 5 Hz (R5, X5, Zr) and the resonant frequency (Fres). Spirometry indices (SI) included forced expiratory volume in 1 sec (FEV₁), forced expiratory flow during the middle half of FVC (FEF_25–75) and forced vital capacity (FVC).
Results: An inverse relationship was observed between raw values of R5, Zr, Fres and SI respectively, and X5 correlated positively with SI. Although significant, these correlations were poor. Receiver operating characteristic curves (ROC) were constructed to identify cutoff points for IOS parameters to discriminate between children according to predefined FEV₁ thresholds (percent predicted), generally used to categorize the level of lung function impairment. No acceptable cutoff points can be found for IOS parameters. Trends analyses in the subgroup of 15 patients showed a significant decline of FEV₁ between the first and the fifth evaluation. None of the IOS indices demonstrated a consistent tendency, apart from a slight decrease of Fres.
Conclusion: IOS measurements presented an insufficient sensitivity to detect and follow bronchial obstruction in CF patients.     

Relationship between disease severity and inflammatory markers in cystic fibrosis.

To evaluate the clinical use of measuring neutrophil, lymphocyte, and eosinophil activities, serum myeloperoxidase (MPO), soluble interleukin-2 receptors (sIL-2R), and eosinophil cationic protein (ECP) were measured in 98 patients with cystic fibrosis and in 85 healthy children. Serum concentrations of MPO, sIL-2R, and ECP were increased in patients with cystic fibrosis (median 807 micrograms/l, 4452 pg/ml, 48.8 micrograms/l, respectively) compared with the controls (median 319 micrograms/l, 2743 pg/ml, 9.4 micrograms/l). ECP concentrations, but not serum MPO or sIL-2R, were significantly related to disease severity assessed by the Shwachman-Kulczycki score and by pulmonary function (forced expiratory volume in one second % predicted). Neither ECP nor sIL-2R was influenced by Pseudomonas aeruginosa infection, acute pulmonary exacerbation, or atopy. Serum MPO, however, was strongly correlated with acute pulmonary exacerbation. In the light of these findings the measurement of serum ECP might thus be used for clinical monitoring and for assessing disease severity in cystic fibrosis. The measurement of serum MPO and sIL-2R did not correlate with the disease severity.